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pharmacokinetics</title> <meta name="description" content="Search results for: pharmacokinetics"> <meta name="keywords" content="pharmacokinetics"> <meta name="viewport" content="width=device-width, initial-scale=1, minimum-scale=1, maximum-scale=1, user-scalable=no"> <meta charset="utf-8"> <link href="https://cdn.waset.org/favicon.ico" type="image/x-icon" rel="shortcut icon"> <link href="https://cdn.waset.org/static/plugins/bootstrap-4.2.1/css/bootstrap.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/plugins/fontawesome/css/all.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/css/site.css?v=150220211555" rel="stylesheet"> </head> <body> <header> <div class="container"> <nav class="navbar navbar-expand-lg navbar-light"> <a class="navbar-brand" href="https://waset.org"> <img src="https://cdn.waset.org/static/images/wasetc.png" alt="Open Science Research Excellence" title="Open Science Research Excellence" /> </a> <button class="d-block d-lg-none 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action="https://publications.waset.org/abstracts/search"> <div id="custom-search-input"> <div class="input-group"> <i class="fas fa-search"></i> <input type="text" class="search-query" name="q" placeholder="Author, Title, Abstract, Keywords" value="pharmacokinetics"> <input type="submit" class="btn_search" value="Search"> </div> </div> </form> </div> </div> <div class="row mt-3"> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Commenced</strong> in January 2007</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Frequency:</strong> Monthly</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Edition:</strong> International</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Paper Count:</strong> 57</div> </div> </div> </div> <h1 class="mt-3 mb-3 text-center" style="font-size:1.6rem;">Search results for: pharmacokinetics</h1> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">57</span> Pharmacokinetics of Oral Controlled-Release Formulation of Doxycycline Hyclate with Polymethacrylate and Acrylic Acid for Dogs</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=S.%20M.%20Arciniegas">S. M. Arciniegas</a>, <a href="https://publications.waset.org/abstracts/search?q=D.%20Vargas"> D. Vargas</a>, <a href="https://publications.waset.org/abstracts/search?q=L.%20Gutierrez"> L. Gutierrez</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The aim of this study was to develop oral drug presentation of doxycycline hyclate that maintains longer therapeutic levels than conventional forms. A polymethacrylate and acrylic acid based matrix were used in different proportions to obtain controlled-release formulations; DOX1 (1:0.25:0.0035), DOX2 (1:2:0.0225) and DOX-C (without excipients). All were tested in vivo in healthy dogs and their serum concentrations vs. time profile was investigated after its oral administration in this species. DOX1 and DOX2 show therapeutic concentrations for 60 hours, while DOX-C only for 24 hours. The pharmacokinetics values tested were K½el, Cmax, Tmax, AUC, AUC∞, AUCt, AUMC, RT, Kel, Vdss, Clb and Frel. DOX1 does not differ significantly from DOX-C, but shows significant differences in all variables with DOX2 (p<0.05). In conclusion, DOX1 presents best pharmacokinetics for time-dependent drug and longer release time of 60 hours, thereby reducing the frequency of administration, the patient's stress, the occurrence of adverse effects and the cost of treatment. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=tetracyclines" title="tetracyclines">tetracyclines</a>, <a href="https://publications.waset.org/abstracts/search?q=long-acting" title=" long-acting"> long-acting</a>, <a href="https://publications.waset.org/abstracts/search?q=sustained-release" title=" sustained-release"> sustained-release</a>, <a href="https://publications.waset.org/abstracts/search?q=carbopol" title=" carbopol"> carbopol</a>, <a href="https://publications.waset.org/abstracts/search?q=eudragit" title=" eudragit"> eudragit</a>, <a href="https://publications.waset.org/abstracts/search?q=canine" title=" canine"> canine</a> </p> <a href="https://publications.waset.org/abstracts/7169/pharmacokinetics-of-oral-controlled-release-formulation-of-doxycycline-hyclate-with-polymethacrylate-and-acrylic-acid-for-dogs" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/7169.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">613</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">56</span> Influence of Menstrual Cycle on the Pharmacokinetics of Antibiotics</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Sandhyarani%20Guggilla">Sandhyarani Guggilla</a> </p> <p class="card-text"><strong>Abstract:</strong></p> For several reasons no two individuals can be considered identical and hence individualization of therapy is the current trend in treating the patients. Influence of menstrual cycle on the pharmacokinetics of Doxycycline. Twelve healthy female volunteers have been included in the study after obtaining written informed consent. The age ranged from 16 to 25 years. Experimental design: The volunteer selection and recruitment will be carried out after obtaining informed consent from each volunteer. The drug administration will be done to each volunteer at 7 a.m along with a glass of water after an overnight fasting on 3rd, 13th and 23rd day of menstrual cycle. These saliva samples will be stored under frozen conditions until HPLC analysis. Results: In the present study the changes in estrogen levels during ovulatory phase have not shown any influence onAUCo-t of Doxycycline. Only AUCo-t of doxycycline showed an increasing trend with increasing levels of estrogen in ovulatory phase, but not in other phases. Even though the FSH levels differed significantly among volunteers during different phases FSH does not seem to influence the overall pharmacokinetic behavior of Doxycycline during different phases. The present study indicated only the trend that the hormone levels may influence the pharmacokinetic behavior of the Doxycycline. Conclusion: In the present study the changes in hormones have shown an increasing C-max, increasing AUCo-t of Doxycycline pharmacokinetics significantly in follicular phase than ovulatory and luteal phases among volunteers during different phases. In other pharmacokinetic properties like clearance, biological half-life, volume of distribution, mean residence time the change was not significant. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=menstrual%20cycle" title="menstrual cycle">menstrual cycle</a>, <a href="https://publications.waset.org/abstracts/search?q=doxycycline" title=" doxycycline"> doxycycline</a>, <a href="https://publications.waset.org/abstracts/search?q=estrogen" title=" estrogen"> estrogen</a>, <a href="https://publications.waset.org/abstracts/search?q=FSH" title=" FSH"> FSH</a>, <a href="https://publications.waset.org/abstracts/search?q=ovulatory%20phase" title=" ovulatory phase "> ovulatory phase </a> </p> <a href="https://publications.waset.org/abstracts/48141/influence-of-menstrual-cycle-on-the-pharmacokinetics-of-antibiotics" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/48141.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">267</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">55</span> Pharmacokinetics, Dosage Regimen and in Vitro Plasma Protein Binding of Danofloxacin following Intravenous Administration in Adult Buffaloes</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Zahid%20Manzoor">Zahid Manzoor</a>, <a href="https://publications.waset.org/abstracts/search?q=Shaukat%20Hussain%20Munawar"> Shaukat Hussain Munawar</a>, <a href="https://publications.waset.org/abstracts/search?q=Zahid%20Iqbal"> Zahid Iqbal</a>, <a href="https://publications.waset.org/abstracts/search?q=Imran%20Ahmad%20Khan"> Imran Ahmad Khan</a>, <a href="https://publications.waset.org/abstracts/search?q=Abdul%20Aziz"> Abdul Aziz</a>, <a href="https://publications.waset.org/abstracts/search?q=Hafiz%20Muhammad%20Qasim"> Hafiz Muhammad Qasim</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=danofloxacin" title="danofloxacin">danofloxacin</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=plasma%20protein%20binding" title=" plasma protein binding"> plasma protein binding</a>, <a href="https://publications.waset.org/abstracts/search?q=buffaloes" title=" buffaloes"> buffaloes</a>, <a href="https://publications.waset.org/abstracts/search?q=dosage%20regimen" title=" dosage regimen"> dosage regimen</a> </p> <a href="https://publications.waset.org/abstracts/21339/pharmacokinetics-dosage-regimen-and-in-vitro-plasma-protein-binding-of-danofloxacin-following-intravenous-administration-in-adult-buffaloes" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/21339.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">610</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">54</span> Pharmacogenetics of Uridine Diphosphate Glucuronosyltransferase (UGT1A9) Genetic Polymorphism on Sodium Valproate Pharmacokinetics in Epilepsy</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Murali%20Munisamy">Murali Munisamy</a>, <a href="https://publications.waset.org/abstracts/search?q=Gauthaman%20Karunakaran"> Gauthaman Karunakaran</a>, <a href="https://publications.waset.org/abstracts/search?q=Mubarak%20Al-Gahtany"> Mubarak Al-Gahtany</a>, <a href="https://publications.waset.org/abstracts/search?q=Vivekanandhan%20Subbiah"> Vivekanandhan Subbiah</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Manjari%20%20Tripati"> M. Manjari Tripati</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=UGT1A9" title="UGT1A9">UGT1A9</a>, <a href="https://publications.waset.org/abstracts/search?q=sodium%20valporate" title=" sodium valporate"> sodium valporate</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacogenetics" title=" pharmacogenetics"> pharmacogenetics</a>, <a href="https://publications.waset.org/abstracts/search?q=polymorphism" title=" polymorphism "> polymorphism </a> </p> <a href="https://publications.waset.org/abstracts/17536/pharmacogenetics-of-uridine-diphosphate-glucuronosyltransferase-ugt1a9-genetic-polymorphism-on-sodium-valproate-pharmacokinetics-in-epilepsy" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/17536.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">425</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">53</span> Determination of Marbofloxacin in Pig Plasma Using LC-MS/MS and Its Application to the Pharmacokinetic Studies</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Jeong%20Woo%20Kang">Jeong Woo Kang</a>, <a href="https://publications.waset.org/abstracts/search?q=MiYoung%20Baek"> MiYoung Baek</a>, <a href="https://publications.waset.org/abstracts/search?q=Ki-Suk%20Kim"> Ki-Suk Kim</a>, <a href="https://publications.waset.org/abstracts/search?q=Kwang-Jick%20Lee"> Kwang-Jick Lee</a>, <a href="https://publications.waset.org/abstracts/search?q=ByungJae%20So"> ByungJae So</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Introduction: A fast, easy and sensitive detection method was developed and validated by liquid chromatography tandem mass spectrometry for the determination of marbofloxacin in pig plasma which was further applied to study the pharmacokinetics of marbofloxacin. Materials and Methods: The plasma sample (500 μL) was mixed with 1.5 ml of 0.1% formic acid in MeCN to precipitate plasma proteins. After shaking for 20 min, The mixture was centrifuged at 5,000 × g for 30 min. It was dried under a nitrogen flow at 50℃. 500 μL aliquot of the sample was injected into the LC-MS/MS system. Chromatographic analysis was carried out mobile phase gradient consisting 0.1% formic acid in D.W. (A) and 0.1% formic acid in MeCN (B) with C18 reverse phase column. Mass spectrometry was performed using the positive ion mode and the selected ion monitoring (MRM). Results and Conclusions: The method validation was performed in the sample matrix. Good linearities (R2>0.999) were observed and the quantified average recoveries of marbofloxacin were 87 - 92% at level of 10 ng g-1 -100 ng g-1. The percent of coefficient of variation (CV) for the described method was less than 10 % over the range of concentrations studied. The limits of detection (LOD) and quantification (LOQ) were 2 and 5 ng g-1, respectively. This method has also been applied successfully to pharmacokinetic analysis of marbofloxacin after intravenous (IV), intramuscular (IM) and oral administration (PO). The mean peak plasma concentration (Cmax) was 2,597 ng g-1at 0.25 h, 2,587 ng g-1at 0.44 h and 2,355 ng g-1at 1.58 h for IV, IM and PO, respectively. The area under the plasma concentration-time curve (AUC0–t) was 24.8, 29.0 and 25.2 h μg/mL for IV, IM and PO, respectively. The elimination half-life (T1/2) was 8.6, 13.1 and 9.5 for IV, IM and PO, respectively. Bioavailability (F) of the marbofloxacin in pig was 117 and 101 % for IM and PO, respectively. Based on these result, marbofloxacin does not have any obstacles as therapeutics to develop the oral formulations such as tablets and capsules. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=marbofloxacin" title="marbofloxacin">marbofloxacin</a>, <a href="https://publications.waset.org/abstracts/search?q=LC-MS%2FMS" title=" LC-MS/MS"> LC-MS/MS</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=chromatographic" title=" chromatographic "> chromatographic </a> </p> <a href="https://publications.waset.org/abstracts/2814/determination-of-marbofloxacin-in-pig-plasma-using-lc-msms-and-its-application-to-the-pharmacokinetic-studies" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/2814.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">548</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">52</span> Pharmacokinetics of First-Line Tuberculosis Drugs in South African Patients from Kwazulu-Natal: Effects of Pharmacogenetic Variation on Rifampicin and Isoniazid Concentrations</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Anushka%20Naidoo">Anushka Naidoo</a>, <a href="https://publications.waset.org/abstracts/search?q=Veron%20Ramsuran"> Veron Ramsuran</a>, <a href="https://publications.waset.org/abstracts/search?q=Maxwell%20Chirehwa"> Maxwell Chirehwa</a>, <a href="https://publications.waset.org/abstracts/search?q=Paolo%20Denti"> Paolo Denti</a>, <a href="https://publications.waset.org/abstracts/search?q=Kogieleum%20Naidoo"> Kogieleum Naidoo</a>, <a href="https://publications.waset.org/abstracts/search?q=Helen%20McIlleron"> Helen McIlleron</a>, <a href="https://publications.waset.org/abstracts/search?q=Nonhlanhla%20Yende-Zuma"> Nonhlanhla Yende-Zuma</a>, <a href="https://publications.waset.org/abstracts/search?q=Ravesh%20Singh"> Ravesh Singh</a>, <a href="https://publications.waset.org/abstracts/search?q=Sinaye%20Ngcapu"> Sinaye Ngcapu</a>, <a href="https://publications.waset.org/abstracts/search?q=Nesri%20Padayatachi"> Nesri Padayatachi </a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=rifampicin" title="rifampicin">rifampicin</a>, <a href="https://publications.waset.org/abstracts/search?q=isoniazid%20pharmacokinetics" title=" isoniazid pharmacokinetics"> isoniazid pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=genetics" title=" genetics"> genetics</a>, <a href="https://publications.waset.org/abstracts/search?q=NAT2" title=" NAT2"> NAT2</a>, <a href="https://publications.waset.org/abstracts/search?q=SLCO1B1" title=" SLCO1B1"> SLCO1B1</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title=" tuberculosis"> tuberculosis</a> </p> <a href="https://publications.waset.org/abstracts/87720/pharmacokinetics-of-first-line-tuberculosis-drugs-in-south-african-patients-from-kwazulu-natal-effects-of-pharmacogenetic-variation-on-rifampicin-and-isoniazid-concentrations" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/87720.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">186</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">51</span> Pharmacokinetic and Tissue Distribution of Etoposide Loaded Modified Glycol Chitosan Nanoparticles</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Akhtar%20Aman">Akhtar Aman</a>, <a href="https://publications.waset.org/abstracts/search?q=Abida%20Raza"> Abida Raza</a>, <a href="https://publications.waset.org/abstracts/search?q=Shumaila%20Bashir"> Shumaila Bashir</a>, <a href="https://publications.waset.org/abstracts/search?q=Mehboob%20Alam"> Mehboob Alam</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=glycol%20chitosan" title="glycol chitosan">glycol chitosan</a>, <a href="https://publications.waset.org/abstracts/search?q=micelles" title=" micelles"> micelles</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=tissue%20distribution" title=" tissue distribution"> tissue distribution</a> </p> <a href="https://publications.waset.org/abstracts/156481/pharmacokinetic-and-tissue-distribution-of-etoposide-loaded-modified-glycol-chitosan-nanoparticles" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/156481.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">104</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">50</span> A Computational Study Concerning the Biological Effects of the Most Commonly Used Phthalates </h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Dana%20Craciun">Dana Craciun</a>, <a href="https://publications.waset.org/abstracts/search?q=Daniela%20Dascalu"> Daniela Dascalu</a>, <a href="https://publications.waset.org/abstracts/search?q=Adriana%20Isvoran"> Adriana Isvoran</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Phthalates are a class of plastic additives that are used to enhance the physical properties of plastics and as solvents in paintings and some of them proved to be of particular concern for the human health. There are insufficient data concerning the health risks of phthalates and further research on evaluating their effects in humans is needed. As humans are not volunteers for such experiments, computational analysis may be used to predict the biological effects of phthalates in humans. Within this study we have used some computational approaches (SwissADME, admetSAR, FAFDrugs) for predicting the absorption, distribution, metabolization, excretion and toxicity (ADME-Tox) profiles and pharmacokinetics for the most common used phthalates. These computational tools are based on quantitative structure-activity relationship modeling approach. The predictions are further compared to the known effects of each considered phthalate in humans and correlations between computational results and experimental data are discussed. Our data revealed that phthalates are a class of compounds reflecting high toxicity both when ingested and when inhaled, but by inhalation their toxicity is even greater. The predicted harmful effects of phthalates are: toxicity and irritations of the respiratory and gastrointestinal tracts, dyspnea, skin and eye irritations and disruption of the functions of liver and of the reproductive system. Many of investigated phthalates are predicted to be able to inhibit some of the cytochromes involved in the metabolism of numerous drugs and consequently to affect the efficiency of administrated treatments for many diseases and to intensify the adverse drugs reactions. The obtained predictions are in good agreement with clinical data concerning the observed effects of some phthalates in cases of acute exposures. Our study emphasizes the possible health effects of numerous phthalates and underlines the applicability of computational methods for predicting the biological effects of xenobiotics. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=phthalates" title="phthalates">phthalates</a>, <a href="https://publications.waset.org/abstracts/search?q=ADME-Tox" title=" ADME-Tox"> ADME-Tox</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=biological%20effects" title=" biological effects"> biological effects</a> </p> <a href="https://publications.waset.org/abstracts/94596/a-computational-study-concerning-the-biological-effects-of-the-most-commonly-used-phthalates" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/94596.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">257</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">49</span> Sceletium Tortuosum: A review on its Phytochemistry, Pharmacokinetics, Biological and Clinical Activities</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Tomi%20Lois%20Olatunji">Tomi Lois Olatunji</a>, <a href="https://publications.waset.org/abstracts/search?q=Frances%20Siebert"> Frances Siebert</a>, <a href="https://publications.waset.org/abstracts/search?q=Ademola%20Emmanuel%20Adetunji"> Ademola Emmanuel Adetunji</a>, <a href="https://publications.waset.org/abstracts/search?q=Brian%20Harvey"> Brian Harvey</a>, <a href="https://publications.waset.org/abstracts/search?q=Johane%20Gericke"> Johane Gericke</a>, <a href="https://publications.waset.org/abstracts/search?q=Josias%20Hamman"> Josias Hamman</a>, <a href="https://publications.waset.org/abstracts/search?q=Frank%20Van%20Der%20Kooy"> Frank Van Der Kooy</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Ethnopharmacological relevance: Sceletium tortuosum (L.) N.E.Br, the most sought after and widely researched species in the genus Sceletium is a succulent forb endemic to South Africa. Traditionally, this medicinal plant is mainly masticated or smoked and used for the relief of toothache, abdominal pain, and as a mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger suppressant, and for its intoxicating/euphoric effects. Sceletium tortuosum is currently of widespread scientific interest due to its clinical potential in treating anxiety and depression, relieving stress in healthy individuals, and enhancing cognitive functions. These pharmacological actions are attributed to its phytochemical constituents referred to as mesembrine-type alkaloids. Aim of the review: The aim of this review was to comprehensively summarize and critically evaluate recent research advances on the phytochemistry, pharmacokinetics, biological and clinical activities of the medicinal plant S. tortuosum. Additionally, current ongoing research and future perspectives are also discussed. Methods: All relevant scientific articles, books, MSc and Ph.D. dissertations on botany, behavioral pharmacology, traditional uses, and phytochemistry of S. tortuosum were retrieved from different databases (including Science Direct, PubMed, Google Scholar, Scopus and Web of Science). For pharmacokinetics and pharmacological effects of S. tortuosum, the focus fell on relevant publications published between 2009 and 2021. Results: Twenty-five alkaloids belonging to four structural classes viz: mesembrine, Sceletium A4, joubertiamine, and tortuosamine, have been identified from S. tortuosum, of which the mesembrine class is predominant. The crude extracts and commercially available standardized extracts of S. tortuosum have displayed a wide spectrum of biological activities (e.g. antimalarial, anti-oxidant, immunomodulatory, anti-HIV, neuroprotection, enhancement of cognitive function) in in vitro or in vivo studies. This plant has not yet been studied in a clinical population, but has potential for enhancing cognitive function, and managing anxiety and depression. Conclusion: As an important South African medicinal plant, S. tortuosum has garnered many research advances on its phytochemistry and biological activities over the last decade. These scientific studies have shown that S. tortuosum has various bioactivities. The findings have further established the link between the phytochemistry and pharmacological application, and support the traditional use of S. tortuosum in the indigenous medicine of South Africa. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=Aizoaceae" title="Aizoaceae">Aizoaceae</a>, <a href="https://publications.waset.org/abstracts/search?q=Mesembrine" title=" Mesembrine"> Mesembrine</a>, <a href="https://publications.waset.org/abstracts/search?q=Serotonin" title=" Serotonin"> Serotonin</a>, <a href="https://publications.waset.org/abstracts/search?q=Sceletium%20tortuosum" title=" Sceletium tortuosum"> Sceletium tortuosum</a>, <a href="https://publications.waset.org/abstracts/search?q=Zembrin%C2%AE" title=" Zembrin®"> Zembrin®</a>, <a href="https://publications.waset.org/abstracts/search?q=psychoactive" title=" psychoactive"> psychoactive</a>, <a href="https://publications.waset.org/abstracts/search?q=antidepressant" title=" antidepressant"> antidepressant</a> </p> <a href="https://publications.waset.org/abstracts/140678/sceletium-tortuosum-a-review-on-its-phytochemistry-pharmacokinetics-biological-and-clinical-activities" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/140678.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">215</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">48</span> Molecular Modeling a Tool for Postulating the Mechanism of Drug Interaction: Glimepiride Alters the Pharmacokinetics of Sildenafil Citrate in Diabetic Nephropathy Animals</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Alok%20Shiomurti%20Tripathi">Alok Shiomurti Tripathi</a>, <a href="https://publications.waset.org/abstracts/search?q=Ajay%20Kumar%20Timiri"> Ajay Kumar Timiri</a>, <a href="https://publications.waset.org/abstracts/search?q=Papiya%20Mitra%20Mazumder"> Papiya Mitra Mazumder</a>, <a href="https://publications.waset.org/abstracts/search?q=Anil%20Chandewar"> Anil Chandewar </a> </p> <p class="card-text"><strong>Abstract:</strong></p> The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=diabetic%20nephropathy" title="diabetic nephropathy">diabetic nephropathy</a>, <a href="https://publications.waset.org/abstracts/search?q=glimepiride" title=" glimepiride"> glimepiride</a>, <a href="https://publications.waset.org/abstracts/search?q=sildenafil%20citrate" title=" sildenafil citrate"> sildenafil citrate</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=homology%20modeling" title=" homology modeling"> homology modeling</a>, <a href="https://publications.waset.org/abstracts/search?q=schrodinger" title=" schrodinger"> schrodinger</a> </p> <a href="https://publications.waset.org/abstracts/39956/molecular-modeling-a-tool-for-postulating-the-mechanism-of-drug-interaction-glimepiride-alters-the-pharmacokinetics-of-sildenafil-citrate-in-diabetic-nephropathy-animals" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/39956.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">378</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">47</span> Pharmacokinetic Modeling of Valsartan in Dog following a Single Oral Administration</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=In-Hwan%20Baek">In-Hwan Baek</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Valsartan is a potent and highly selective antagonist of the angiotensin II type 1 receptor, and is widely used for the treatment of hypertension. The aim of this study was to investigate the pharmacokinetic properties of the valsartan in dogs following oral administration of a single dose using quantitative modeling approaches. Forty beagle dogs were randomly divided into two group. Group A (n=20) was administered a single oral dose of valsartan 80 mg (Diovan® 80 mg), and group B (n=20) was administered a single oral dose of valsartan 160 mg (Diovan® 160 mg) in the morning after an overnight fast. Blood samples were collected into heparinized tubes before and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 h following oral administration. The plasma concentrations of the valsartan were determined using LC-MS/MS. Non-compartmental pharmacokinetic analyses were performed using WinNonlin Standard Edition software, and modeling approaches were performed using maximum-likelihood estimation via the expectation maximization (MLEM) algorithm with sampling using ADAPT 5 software. After a single dose of valsartan 80 mg, the mean value of maximum concentration (Cmax) was 2.68 ± 1.17 μg/mL at 1.83 ± 1.27 h. The area under the plasma concentration-versus-time curve from time zero to the last measurable concentration (AUC24h) value was 13.21 ± 6.88 μg·h/mL. After dosing with valsartan 160 mg, the mean Cmax was 4.13 ± 1.49 μg/mL at 1.80 ± 1.53 h, the AUC24h was 26.02 ± 12.07 μg·h/mL. The Cmax and AUC values increased in proportion to the increment in valsartan dose, while the pharmacokinetic parameters of elimination rate constant, half-life, apparent of total clearance, and apparent of volume of distribution were not significantly different between the doses. Valsartan pharmacokinetic analysis fits a one-compartment model with first-order absorption and elimination following a single dose of valsartan 80 mg and 160 mg. In addition, high inter-individual variability was identified in the absorption rate constant. In conclusion, valsartan displays the dose-dependent pharmacokinetics in dogs, and Subsequent quantitative modeling approaches provided detailed pharmacokinetic information of valsartan. The current findings provide useful information in dogs that will aid future development of improved formulations or fixed-dose combinations. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=dose-dependent" title="dose-dependent">dose-dependent</a>, <a href="https://publications.waset.org/abstracts/search?q=modeling" title=" modeling"> modeling</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=valsartan" title=" valsartan"> valsartan</a> </p> <a href="https://publications.waset.org/abstracts/67162/pharmacokinetic-modeling-of-valsartan-in-dog-following-a-single-oral-administration" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/67162.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">297</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">46</span> Determination of the Phytochemicals Composition and Pharmacokinetics of whole Coffee Fruit Caffeine Extract by Liquid Chromatography-Tandem Mass Spectrometry</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Boris%20Nemzer">Boris Nemzer</a>, <a href="https://publications.waset.org/abstracts/search?q=Nebiyu%20Abshiru"> Nebiyu Abshiru</a>, <a href="https://publications.waset.org/abstracts/search?q=Z.%20B.%20Pietrzkowski"> Z. B. Pietrzkowski</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Coffee cherry is one of the most ubiquitous agricultural commodities which possess nutritional and human health beneficial properties. Between the two most widely used coffee cherries Coffea arabica (Arabica) and Coffea canephora (Robusta), Coffea arabica remains superior due to its sensory properties and, therefore, remains in great demand in the global coffee market. In this study, the phytochemical contents and pharmacokinetics of Coffeeberry® Energy (CBE), a commercially available Arabica whole coffee fruit caffeine extract, are investigated. For phytochemical screening, 20 mg of CBE was dissolved in an aqueous methanol solution for analysis by mass spectrometry (MS). Quantification of caffeine and chlorogenic acids (CGAs) contents of CBE was performed using HPLC. For the bioavailability study, serum samples were collected from human subjects before and after 1, 2 and 3 h post-ingestion of 150mg CBE extract. Protein precipitation and extraction were carried out using methanol. Identification of compounds was performed using an untargeted metabolomic approach on Q-Exactive Orbitrap MS coupled to reversed-phase chromatography. Data processing was performed using Thermo Scientific Compound Discover 3.3 software. Phytochemical screening identified a total of 170 compounds, including organic acids, phenolic acids, CGAs, diterpenoids and hydroxytryptamine. Caffeine & CGAs make up more than, respectively, 70% & 9% of the total CBE composition. For serum samples, a total of 82 metabolites representing 32 caffeine- and 50 phenolic-derived metabolites were identified. Volcano plot analysis revealed 32 differential metabolites (24 caffeine- and 8 phenolic-derived) that showed an increase in serum level post-CBE dosing. Caffeine, uric acid, and trimethyluric acid isomers exhibited 4- to 10-fold increase in serum abundance post-dosing. 7-Methyluric acid, 1,7-dimethyluric acid, paraxanthine and theophylline exhibited a minimum of 1.5-fold increase in serum level. Among the phenolic-derived metabolites, iso-feruloyl quinic acid isomers (3-, 4- and 5-iFQA) showed the highest increase in serum level. These compounds were essentially absent in serum collected before dosage. More interestingly, the iFQA isomers were not originally present in the CBE extract, as our phytochemical screen did not identify these compounds. This suggests the potential formation of the isomers during the digestion and absorption processes. Pharmacokinetics parameters (Cmax, Tmax and AUC0-3h) of caffeine- and phenolic-derived metabolites were also investigated. Caffeine was rapidly absorbed, reaching a maximum concentration (Cmax) of 10.95 µg/ml in just 1 hour. Thereafter, caffeine level steadily dropped from the peak level, although it did not return to baseline within the 3-hour dosing period. The disappearance of caffeine from circulation was mirrored by the rise in the concentration of its methylxanthine metabolites. Similarly, serum concentration of iFQA isomers steadily increased, reaching maximum (Cmax: 3-iFQA, 1.54 ng/ml; 4-iFQA, 2.47 ng/ml; 5-iFQA, 2.91 ng/ml) at tmax of 1.5 hours. The isomers remained well above the baseline during the 3-hour dosing period, allowing them to remain in circulation long enough for absorption into the body. Overall, the current study provides evidence of the potential health benefits of a uniquely formulated whole coffee fruit product. Consumption of this product resulted in a distinct serum profile of bioactive compounds, as demonstrated by the more than 32 metabolites that exhibited a significant change in systemic exposure. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=phytochemicals" title="phytochemicals">phytochemicals</a>, <a href="https://publications.waset.org/abstracts/search?q=mass%20spectrometry" title=" mass spectrometry"> mass spectrometry</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=differential%20metabolites" title=" differential metabolites"> differential metabolites</a>, <a href="https://publications.waset.org/abstracts/search?q=chlorogenic%20acids" title=" chlorogenic acids"> chlorogenic acids</a> </p> <a href="https://publications.waset.org/abstracts/160767/determination-of-the-phytochemicals-composition-and-pharmacokinetics-of-whole-coffee-fruit-caffeine-extract-by-liquid-chromatography-tandem-mass-spectrometry" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/160767.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">68</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">45</span> Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Suliman%20Al-Fayoumi">Suliman Al-Fayoumi</a>, <a href="https://publications.waset.org/abstracts/search?q=Sherri%20Amberg"> Sherri Amberg</a>, <a href="https://publications.waset.org/abstracts/search?q=Huafeng%20Zhou"> Huafeng Zhou</a>, <a href="https://publications.waset.org/abstracts/search?q=Jack%20W.%20Singer"> Jack W. Singer</a>, <a href="https://publications.waset.org/abstracts/search?q=James%20P.%20Dean"> James P. Dean</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=pacritinib" title="pacritinib">pacritinib</a>, <a href="https://publications.waset.org/abstracts/search?q=myelofibrosis" title=" myelofibrosis"> myelofibrosis</a>, <a href="https://publications.waset.org/abstracts/search?q=hepatic%20impairment" title=" hepatic impairment"> hepatic impairment</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a> </p> <a href="https://publications.waset.org/abstracts/43510/pharmacokinetics-and-safety-of-pacritinib-in-patients-with-hepatic-impairment-and-healthy-volunteers" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/43510.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">298</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">44</span> Assessing the Impact of Antiretroviral Mediated Drug-Drug Interactions on Piperaquine Antimalarial Treatment in Pregnant Women Using Physiologically Based Pharmacokinetic Modelling</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Olusola%20Omolola%20Olafuyi">Olusola Omolola Olafuyi</a>, <a href="https://publications.waset.org/abstracts/search?q=Michael%20Coleman"> Michael Coleman</a>, <a href="https://publications.waset.org/abstracts/search?q=Raj%20Kumar%20Singh%20Badhan"> Raj Kumar Singh Badhan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Introduction: Malaria in pregnancy has morbidity and mortality implication on both mother and unborn child. Piperaquine (PQ) based antimalarial treatment is emerging as a choice antimalarial for pregnant women in the face of resistance to current antimalarial treatment recommendation in pregnancy. Physiological and biochemical changes in pregnant women may affect the pharmacokinetics of the antimalarial drug in these. In malaria endemic regions other infectious diseases like HIV/AIDs are prevalent. Pregnant women who are co-infected with malaria and HIV/AID are at even more greater risk of death not only due to complications of the diseases but also due to drug-drug interactions (DDIs) between antimalarials (AMT) and antiretroviral (ARVs). In this study, physiologically based pharmacokinetic (PBPK) modelling was used to investigate the effect of physiological and biochemical changes on the impact of ARV mediated DDIs in pregnant women in three countries. Method: A PBPK model for PQ was developed on SimCYP® using published physicochemical and pharmacokinetic data of PQ from literature, this was validated in three customized population groups from Thailand, Sudan and Papua New Guinea with clinical data. Validation of PQ model was also done in presence of interaction with efavirenz (pre-validated on SimCYP®). Different albumin levels and pregnancy stages was simulated in the presence of interaction with standard doses of efavirenz and ritonavir. PQ day 7 concentration of 30ng/ml was used as the efficacy endpoint for PQ treatment.. Results: The median day 7 concentration of PQ remained virtually consistent throughout pregnancy and were satisfactory across the three population groups ranging from 26-34.1ng/ml; this implied the efficacy of PQ throughout pregnancy. DDI interaction with ritonavir and efavirenz resulted in modest effect on the day 7 concentrations of PQ with AUCratio ranging from 0.56-0.8 and 1.64-1.79 for efavirenz and ritonavir respectively over 10-40 gestational weeks, however, a reduction in human serum albumin level reflective of severe malaria resulted in significantly reduced the number of subjects attaining the PQ day 7 concentration in the presence of both DDIs. The model demonstrated that the DDI between PQ and ARV in pregnant women with different malaria severities can alter the pharmacokinetic of PQ. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=antiretroviral" title="antiretroviral">antiretroviral</a>, <a href="https://publications.waset.org/abstracts/search?q=malaria" title=" malaria"> malaria</a>, <a href="https://publications.waset.org/abstracts/search?q=piperaquine" title=" piperaquine"> piperaquine</a>, <a href="https://publications.waset.org/abstracts/search?q=pregnancy" title=" pregnancy"> pregnancy</a>, <a href="https://publications.waset.org/abstracts/search?q=physiologically-based%20pharmacokinetics" title=" physiologically-based pharmacokinetics"> physiologically-based pharmacokinetics</a> </p> <a href="https://publications.waset.org/abstracts/72751/assessing-the-impact-of-antiretroviral-mediated-drug-drug-interactions-on-piperaquine-antimalarial-treatment-in-pregnant-women-using-physiologically-based-pharmacokinetic-modelling" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/72751.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">185</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">43</span> Efficacy of Opicapone and Levodopa with Different Levodopa Daily Doses in Parkinson’s Disease Patients with Early Motor Fluctuations: Findings from the Korean ADOPTION Study</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Jee-Young%20Lee">Jee-Young Lee</a>, <a href="https://publications.waset.org/abstracts/search?q=Joaquim%20J.%20Ferreira"> Joaquim J. Ferreira</a>, <a href="https://publications.waset.org/abstracts/search?q=Hyeo-il%20Ma"> Hyeo-il Ma</a>, <a href="https://publications.waset.org/abstracts/search?q=Jos%C3%A9-Francisco%20Rocha"> José-Francisco Rocha</a>, <a href="https://publications.waset.org/abstracts/search?q=Beomseok%20Jeon"> Beomseok Jeon</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The effective management of wearing-off is a key driver of medication changes for patients with Parkinson’s disease (PD) treated with levodopa (L-DOPA). While L-DOPA is well tolerated and efficacious, its clinical utility over time is often limited by the development of complications such as dyskinesia. Still, common first-line option includes adjusting the daily L-DOPA dose followed by adjunctive therapies usually counting for the L-DOPA equivalent daily dose (LEDD). The LEDD conversion formulae are a tool used to compare the equivalence of anti-PD medications. The aim of this work is to compare the effects of opicapone (OPC) 50 mg, a catechol-O-methyltransferase (COMT) inhibitor, and an additional 100 mg dose of L-DOPA in reducing the off time in PD patients with early motor fluctuations receiving different daily L-DOPA doses. OPC was found to be well tolerated and efficacious in advanced PD population. This work utilized patients' home diary data from a 4-week Phase 2 pharmacokinetics clinical study. The Korean ADOPTION study randomized (1:1) patients with PD and early motor fluctuations treated with up to 600 mg of L-DOPA given 3–4 times daily. The main endpoint was change from baseline in off time in the subgroup of patients receiving 300–400 mg/day L-DOPA at baseline plus OPC 50 mg and in the subgroup receiving >300 mg/day L-DOPA at baseline plus an additional dose of L-DOPA 100 mg. Of the 86 patients included in this subgroup analysis, 39 received OPC 50 mg and 47 L-DOPA 100 mg. At baseline, both L-DOPA total daily dose and LEDD were lower in the L-DOPA 300–400 mg/day plus OPC 50 mg group than in the L-DOPA >300 mg/day plus L-DOPA 100 mg. However, at Week 4, LEDD was similar between the two groups. The mean (±standard error) reduction in off time was approximately three-fold greater for the OPC 50 mg than for the L-DOPA 100 mg group, being -63.0 (14.6) minutes for patients treated with L-DOPA 300–400 mg/day plus OPC 50 mg, and -22.1 (9.3) minutes for those receiving L-DOPA >300 mg/day plus L-DOPA 100 mg. In conclusion, despite similar LEDD, OPC demonstrated a significantly greater reduction in off time when compared to an additional 100 mg L-DOPA dose. The effect of OPC appears to be LEDD independent, suggesting that caution should be exercised when employing LEDD to guide treatment decisions as this does not take into account the timing of each dose, onset, duration of therapeutic effect and individual responsiveness. Additionally, OPC could be used for keeping the L-DOPA dose as low as possible for as long as possible to avoid the development of motor complications which are a significant source of disability. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=opicapone" title="opicapone">opicapone</a>, <a href="https://publications.waset.org/abstracts/search?q=levodopa" title=" levodopa"> levodopa</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=off-time" title=" off-time"> off-time</a> </p> <a href="https://publications.waset.org/abstracts/184293/efficacy-of-opicapone-and-levodopa-with-different-levodopa-daily-doses-in-parkinsons-disease-patients-with-early-motor-fluctuations-findings-from-the-korean-adoption-study" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/184293.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">62</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">42</span> Population Pharmacokinetics of Levofloxacin and Moxifloxacin, and the Probability of Target Attainment in Ethiopian Patients with Multi-Drug Resistant Tuberculosis</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Temesgen%20Sidamo">Temesgen Sidamo</a>, <a href="https://publications.waset.org/abstracts/search?q=Prakruti%20S.%20Rao"> Prakruti S. Rao</a>, <a href="https://publications.waset.org/abstracts/search?q=Eleni%20Akllilu"> Eleni Akllilu</a>, <a href="https://publications.waset.org/abstracts/search?q=Workineh%20Shibeshi"> Workineh Shibeshi</a>, <a href="https://publications.waset.org/abstracts/search?q=Yumi%20Park"> Yumi Park</a>, <a href="https://publications.waset.org/abstracts/search?q=Yong-Soon%20Cho"> Yong-Soon Cho</a>, <a href="https://publications.waset.org/abstracts/search?q=Jae-Gook%20Shin"> Jae-Gook Shin</a>, <a href="https://publications.waset.org/abstracts/search?q=Scott%20K.%20Heysell"> Scott K. Heysell</a>, <a href="https://publications.waset.org/abstracts/search?q=Stellah%20G.%20Mpagama"> Stellah G. Mpagama</a>, <a href="https://publications.waset.org/abstracts/search?q=Ephrem%20Engidawork"> Ephrem Engidawork</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=population%20PK" title="population PK">population PK</a>, <a href="https://publications.waset.org/abstracts/search?q=PTA" title=" PTA"> PTA</a>, <a href="https://publications.waset.org/abstracts/search?q=moxifloxacin" title=" moxifloxacin"> moxifloxacin</a>, <a href="https://publications.waset.org/abstracts/search?q=levofloxacin" title=" levofloxacin"> levofloxacin</a>, <a href="https://publications.waset.org/abstracts/search?q=MDR-TB%20patients" title=" MDR-TB patients"> MDR-TB patients</a>, <a href="https://publications.waset.org/abstracts/search?q=ethiopia" title=" ethiopia"> ethiopia</a> </p> <a href="https://publications.waset.org/abstracts/151034/population-pharmacokinetics-of-levofloxacin-and-moxifloxacin-and-the-probability-of-target-attainment-in-ethiopian-patients-with-multi-drug-resistant-tuberculosis" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/151034.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">120</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">41</span> Bioanalytical Method Development and Validation of Aminophylline in Rat Plasma Using Reverse Phase High Performance Liquid Chromatography: An Application to Preclinical Pharmacokinetics</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=S.%20G.%20Vasantharaju">S. G. Vasantharaju</a>, <a href="https://publications.waset.org/abstracts/search?q=Viswanath%20Guptha"> Viswanath Guptha</a>, <a href="https://publications.waset.org/abstracts/search?q=Raghavendra%20Shetty"> Raghavendra Shetty</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Introduction: Aminophylline is a methylxanthine derivative belonging to the class bronchodilator. From the literature survey, reported methods reveals the solid phase extraction and liquid liquid extraction which is highly variable, time consuming, costly and laborious analysis. Present work aims to develop a simple, highly sensitive, precise and accurate high-performance liquid chromatography method for the quantification of Aminophylline in rat plasma samples which can be utilized for preclinical studies. Method: Reverse Phase high-performance liquid chromatography method. Results: Selectivity: Aminophylline and the internal standard were well separated from the co-eluted components and there was no interference from the endogenous material at the retention time of analyte and the internal standard. The LLOQ measurable with acceptable accuracy and precision for the analyte was 0.5 µg/mL. Linearity: The developed and validated method is linear over the range of 0.5-40.0 µg/mL. The coefficient of determination was found to be greater than 0.9967, indicating the linearity of this method. Accuracy and precision: The accuracy and precision values for intra and inter day studies at low, medium and high quality control samples concentrations of aminophylline in the plasma were within the acceptable limits Extraction recovery: The method produced consistent extraction recovery at all 3 QC levels. The mean extraction recovery of aminophylline was 93.57 ± 1.28% while that of internal standard was 90.70 ± 1.30%. Stability: The results show that aminophylline is stable in rat plasma under the studied stability conditions and that it is also stable for about 30 days when stored at -80˚C. Pharmacokinetic studies: The method was successfully applied to the quantitative estimation of aminophylline rat plasma following its oral administration to rats. Discussion: Preclinical studies require a rapid and sensitive method for estimating the drug concentration in the rat plasma. The method described in our article includes a simple protein precipitation extraction technique with ultraviolet detection for quantification. The present method is simple and robust for fast high-throughput sample analysis with less analysis cost for analyzing aminophylline in biological samples. In this proposed method, no interfering peaks were observed at the elution times of aminophylline and the internal standard. The method also had sufficient selectivity, specificity, precision and accuracy over the concentration range of 0.5 - 40.0 µg/mL. An isocratic separation technique was used underlining the simplicity of the presented method. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=Aminophyllin" title="Aminophyllin">Aminophyllin</a>, <a href="https://publications.waset.org/abstracts/search?q=preclinical%20pharmacokinetics" title=" preclinical pharmacokinetics"> preclinical pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=rat%20plasma" title=" rat plasma"> rat plasma</a>, <a href="https://publications.waset.org/abstracts/search?q=RPHPLC" title=" RPHPLC"> RPHPLC</a> </p> <a href="https://publications.waset.org/abstracts/64169/bioanalytical-method-development-and-validation-of-aminophylline-in-rat-plasma-using-reverse-phase-high-performance-liquid-chromatography-an-application-to-preclinical-pharmacokinetics" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/64169.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">222</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">40</span> The Influence of Gender on Itraconazole Pharmacokinetic Parameters in Healthy Adults</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Milijana%20N.%20Miljkovic">Milijana N. Miljkovic</a>, <a href="https://publications.waset.org/abstracts/search?q=Viktorija%20M.%20Dragojevic-Simic"> Viktorija M. Dragojevic-Simic</a>, <a href="https://publications.waset.org/abstracts/search?q=Nemanja%20K.%20Rancic"> Nemanja K. Rancic</a>, <a href="https://publications.waset.org/abstracts/search?q=Vesna%20M.%20Jacevic"> Vesna M. Jacevic</a>, <a href="https://publications.waset.org/abstracts/search?q=Snezana%20B.%20Djordjevic"> Snezana B. Djordjevic</a>, <a href="https://publications.waset.org/abstracts/search?q=Momir%20M.%20Mikov"> Momir M. Mikov</a>, <a href="https://publications.waset.org/abstracts/search?q=Aleksandra%20M.%20Kovacevic"> Aleksandra M. Kovacevic</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=itraconazole" title="itraconazole">itraconazole</a>, <a href="https://publications.waset.org/abstracts/search?q=gender" title=" gender"> gender</a>, <a href="https://publications.waset.org/abstracts/search?q=hydroxyitraconazole" title=" hydroxyitraconazole"> hydroxyitraconazole</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a> </p> <a href="https://publications.waset.org/abstracts/117538/the-influence-of-gender-on-itraconazole-pharmacokinetic-parameters-in-healthy-adults" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/117538.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">137</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">39</span> Pharmacokinetic Monitoring of Glimepiride and Ilaprazole in Rat Plasma by High Performance Liquid Chromatography with Diode Array Detection</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Anil%20P.%20Dewani">Anil P. Dewani</a>, <a href="https://publications.waset.org/abstracts/search?q=Alok%20S.%20Tripathi"> Alok S. Tripathi</a>, <a href="https://publications.waset.org/abstracts/search?q=Anil%20V.%20Chandewar"> Anil V. Chandewar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Present manuscript reports the development and validation of a quantitative high performance liquid chromatography method for the pharmacokinetic evaluation of Glimepiride (GLM) and Ilaprazole (ILA) in rat plasma. The plasma samples were involved with Solid phase extraction process (SPE). The analytes were resolved on a Phenomenex C18 column (4.6 mm× 250 mm; 5 µm particle size) using a isocratic elution mode comprising methanol:water (80:20 % v/v) with pH of water modified to 3 using Formic acid, the total run time was 10 min at 225 nm as common wavelength, the flow rate throughout was 1ml/min. The method was validated over the concentration range from 10 to 600 ng/mL for GLM and ILA, in rat plasma. Metformin (MET) was used as Internal Standard. Validation data demonstrated the method to be selective, sensitive, accurate and precise. The limit of detection was 1.54 and 4.08 and limit of quantification was 5.15 and 13.62 for GLM and ILA respectively, the method demonstrated excellent linearity with correlation coefficients (r2) 0.999. The intra and inter-day precision (RSD%) values were < 2.0% for both ILA and GLM. The method was successfully applied in pharmacokinetic studies followed by oral administration in rats. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title="pharmacokinetics">pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=glimepiride" title=" glimepiride"> glimepiride</a>, <a href="https://publications.waset.org/abstracts/search?q=ilaprazole" title=" ilaprazole"> ilaprazole</a>, <a href="https://publications.waset.org/abstracts/search?q=HPLC" title=" HPLC"> HPLC</a>, <a href="https://publications.waset.org/abstracts/search?q=SPE" title=" SPE"> SPE</a> </p> <a href="https://publications.waset.org/abstracts/40102/pharmacokinetic-monitoring-of-glimepiride-and-ilaprazole-in-rat-plasma-by-high-performance-liquid-chromatography-with-diode-array-detection" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/40102.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">369</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">38</span> The Discussion of Peritoneal Dialysis Patients Taking Proper Portion of Valacyclovir</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Wan%20Shan%20Chiang">Wan Shan Chiang</a>, <a href="https://publications.waset.org/abstracts/search?q=Charn%20Ting%20Wang"> Charn Ting Wang</a>, <a href="https://publications.waset.org/abstracts/search?q=Wei-Chih%20Kan"> Wei-Chih Kan</a>, <a href="https://publications.waset.org/abstracts/search?q=Hui-Chen%20Huang"> Hui-Chen Huang</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Dialysis patients have risk in Zoster virus because of low immune. Valacyclovir (product name: Valtex) 500mg/tab, an anti-zoster virus medicine, is digested in kidney and it has side-effect of nervous system in patients with malfunction kidneys. Although the clinical basis of the proposed administration, we found that patients still have side effects. So we want to explore the appropriate dose of peritoneal dialysis patients. We read small samples of case reports and analyze 8 cases in our hospital, some patients’ Kt/v, match the standard of dialysis, and still go to the toilet, they still have side effect seriously with 500mg portion. The solution to this includes stopping medicine, reduction of medicine, increase of liquid change and timely hemodialysis and all of them speed up the recovery. The safety of medication needs extra attention of medical care employee. If they can tell the doctor if the patient has urine or not in his or her Kt/v, the doctor can prescribe the medicine accordingly. About the limitation, due to the lack of cases and related pharmacokinetics numbers. Therefore, for peritoneal patients, we think 500mg/48hoursis the saves. We also want to remind pharmaceuticals to revise the portion taken by patients, so that the doctor may judge the use. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=herpes%20zoster" title="herpes zoster">herpes zoster</a>, <a href="https://publications.waset.org/abstracts/search?q=Valacyclovir" title=" Valacyclovir"> Valacyclovir</a>, <a href="https://publications.waset.org/abstracts/search?q=peritoneal%20dialysis" title=" peritoneal dialysis"> peritoneal dialysis</a>, <a href="https://publications.waset.org/abstracts/search?q=health%20education" title=" health education"> health education</a> </p> <a href="https://publications.waset.org/abstracts/82095/the-discussion-of-peritoneal-dialysis-patients-taking-proper-portion-of-valacyclovir" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/82095.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">314</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">37</span> Phytochemicals from Enantia Chlorantha Stem Bark Inhibits the Activity ?-Amylase and ?-Glucosidase: Molecular Docking Studies</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Hammed%20Tanimowo%20Aiyelabegan">Hammed Tanimowo Aiyelabegan</a>, <a href="https://publications.waset.org/abstracts/search?q=Oluchukwu%20Franklin%20Aladi"> Oluchukwu Franklin Aladi</a>, <a href="https://publications.waset.org/abstracts/search?q=Mutiu%20Adewumi%20Alabi"> Mutiu Adewumi Alabi</a>, <a href="https://publications.waset.org/abstracts/search?q=Raliat%20Abimbola%20Aladodo"> Raliat Abimbola Aladodo</a>, <a href="https://publications.waset.org/abstracts/search?q=Emmanuel%20Oladipupo%20Ajani"> Emmanuel Oladipupo Ajani</a>, <a href="https://publications.waset.org/abstracts/search?q=Abdulganiyu%20Giwa"> Abdulganiyu Giwa</a>, <a href="https://publications.waset.org/abstracts/search?q=Esther%20Owolabi"> Esther Owolabi</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The study aimed to evaluate the inhibitory activities of ligands from Enantia chlorantha stem bark on α-amylase and α-glucosidase. In silico pharmacokinetic properties and docking scores were employed to analyse the inhibition using SwissADME and Autodock4.2, respectively. Results revealed that drug-likeness, pharmacokinetics and bioavailability radar of all the ligands except jatrorrhizine and acarbose falls within the radar according to the Lipinski rule of 5. The binding energies of the protein-ligand interactions also show that the ligand fits into the active site. The results obtained from this study show that the chemical constituents from Enantia chlorantha stem bark may bring about positive physiological changes in a patient suffering from diabetes mellitus. Further in vitro studies on diabetes cell lines and in vivo studies on the animal may validate these compounds for diabetes treatment. These phytoconstituents could help in the development of novel anti-diabetic molecules. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=diabetes%20mellitus" title="diabetes mellitus">diabetes mellitus</a>, <a href="https://publications.waset.org/abstracts/search?q=%3F-amylase" title=" ?-amylase"> ?-amylase</a>, <a href="https://publications.waset.org/abstracts/search?q=%3F-glucosidase" title=" ?-glucosidase"> ?-glucosidase</a>, <a href="https://publications.waset.org/abstracts/search?q=in%20silico" title=" in silico"> in silico</a>, <a href="https://publications.waset.org/abstracts/search?q=Enantia%20chlorantha%20stem%20bark" title=" Enantia chlorantha stem bark"> Enantia chlorantha stem bark</a> </p> <a href="https://publications.waset.org/abstracts/145916/phytochemicals-from-enantia-chlorantha-stem-bark-inhibits-the-activity-amylase-and-glucosidase-molecular-docking-studies" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/145916.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">172</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">36</span> Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Ozturk">Narin Ozturk</a>, <a href="https://publications.waset.org/abstracts/search?q=Xiao-Mei%20Li"> Xiao-Mei Li</a>, <a href="https://publications.waset.org/abstracts/search?q=Sylvie%20Giachetti"> Sylvie Giachetti</a>, <a href="https://publications.waset.org/abstracts/search?q=Francis%20Levi"> Francis Levi</a>, <a href="https://publications.waset.org/abstracts/search?q=Alper%20Okyar"> Alper Okyar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=circadian%20rhythm" title="circadian rhythm">circadian rhythm</a>, <a href="https://publications.waset.org/abstracts/search?q=chronotoxicity" title=" chronotoxicity"> chronotoxicity</a>, <a href="https://publications.waset.org/abstracts/search?q=everolimus" title=" everolimus"> everolimus</a>, <a href="https://publications.waset.org/abstracts/search?q=mdr1a%3A%3ALuc%20mice" title=" mdr1a::Luc mice"> mdr1a::Luc mice</a>, <a href="https://publications.waset.org/abstracts/search?q=p-glycoprotein" title=" p-glycoprotein"> p-glycoprotein</a> </p> <a href="https://publications.waset.org/abstracts/71521/relevance-of-dosing-time-for-everolimus-toxicity-in-respect-to-the-circadian-p-glycoprotein-expression-in-mdr1aluc-mice" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/71521.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">342</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">35</span> Smart Polymeric Nanoparticles Loaded with Vincristine Sulfate for Applications in Breast Cancer Drug Delivery in MDA-MB 231 and MCF7 Cell Lines</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Reynaldo%20Esquivel">Reynaldo Esquivel</a>, <a href="https://publications.waset.org/abstracts/search?q=Pedro%20Hernandez"> Pedro Hernandez</a>, <a href="https://publications.waset.org/abstracts/search?q=Aaron%20Martinez-Higareda"> Aaron Martinez-Higareda</a>, <a href="https://publications.waset.org/abstracts/search?q=Sergio%20Tena-Cano"> Sergio Tena-Cano</a>, <a href="https://publications.waset.org/abstracts/search?q=Enrique%20Alvarez-Ramos"> Enrique Alvarez-Ramos</a>, <a href="https://publications.waset.org/abstracts/search?q=Armando%20Lucero-Acuna"> Armando Lucero-Acuna </a> </p> <p class="card-text"><strong>Abstract:</strong></p> Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=nanoparticles" title="nanoparticles">nanoparticles</a>, <a href="https://publications.waset.org/abstracts/search?q=vincristine" title=" vincristine"> vincristine</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20delivery" title=" drug delivery"> drug delivery</a>, <a href="https://publications.waset.org/abstracts/search?q=PNIPAM" title=" PNIPAM"> PNIPAM</a> </p> <a href="https://publications.waset.org/abstracts/90050/smart-polymeric-nanoparticles-loaded-with-vincristine-sulfate-for-applications-in-breast-cancer-drug-delivery-in-mda-mb-231-and-mcf7-cell-lines" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/90050.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">156</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">34</span> A Validated UPLC-MS/MS Assay Using Negative Ionization Mode for High-Throughput Determination of Pomalidomide in Rat Plasma </h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Muzaffar%20Iqbal">Muzaffar Iqbal</a>, <a href="https://publications.waset.org/abstracts/search?q=Essam%20Ezzeldin"> Essam Ezzeldin</a>, <a href="https://publications.waset.org/abstracts/search?q=Khalid%20A.%20Al-Rashood"> Khalid A. Al-Rashood </a> </p> <p class="card-text"><strong>Abstract:</strong></p> Pomalidomide is a second generation oral immunomodulatory agent, being used for the treatment of multiple myeloma in patients with disease refractory to lenalidomide and bortezomib. In this study, a sensitive UPLC-MS/MS assay was developed and validated for high-throughput determination of pomalidomide in rat plasma using celecoxib as an internal standard (IS). Liquid liquid extraction using dichloromethane as extracting agent was employed to extract pomalidomide and IS from 200 µL of plasma. Chromatographic separation was carried on Acquity BEHTM C18 column (50 × 2.1 mm, 1.7 µm) using an isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v), at a flow rate of 0.250 mL/min. Both pomalidomide and IS were eluted at 0.66 ± 0.03 and 0.80 ± 0.03 min, respectively with a total run time of 1.5 min only. Detection was performed on a triple quadrupole tandem mass spectrometer using electrospray ionization in negative mode. The precursor to product ion transitions of m/z 272.01 → 160.89 for pomalidomide and m/z 380.08 → 316.01 for IS were used to quantify them respectively, using multiple reaction monitoring mode. The developed method was validated according to regulatory guideline for bioanalytical method validation. The linearity in plasma sample was achieved in the concentration range of 0.47–400 ng/mL (r2 ≥ 0.997). The intra and inter-day precision values were ≤ 11.1% (RSD, %) whereas accuracy values ranged from - 6.8 – 8.5% (RE, %). In addition, other validation results were within the acceptance criteria and the method was successfully applied in a pharmacokinetic study of pomalidomide in rats. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=pomalidomide" title="pomalidomide">pomalidomide</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=LC-MS%2FMS" title=" LC-MS/MS"> LC-MS/MS</a>, <a href="https://publications.waset.org/abstracts/search?q=celecoxib" title=" celecoxib "> celecoxib </a> </p> <a href="https://publications.waset.org/abstracts/20277/a-validated-uplc-msms-assay-using-negative-ionization-mode-for-high-throughput-determination-of-pomalidomide-in-rat-plasma" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/20277.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">391</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">33</span> Development of Lipid Architectonics for Improving Efficacy and Ameliorating the Oral Bioavailability of Elvitegravir </h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Bushra%20Nabi">Bushra Nabi</a>, <a href="https://publications.waset.org/abstracts/search?q=Saleha%20Rehman"> Saleha Rehman</a>, <a href="https://publications.waset.org/abstracts/search?q=Sanjula%20Baboota"> Sanjula Baboota</a>, <a href="https://publications.waset.org/abstracts/search?q=Javed%20Ali"> Javed Ali</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Aim: The objective of research undertaken is analytical method validation (HPLC method) of an anti-HIV drug Elvitegravir (EVG). Additionally carrying out the forced degradation studies of the drug under different stress conditions to determine its stability. It is envisaged in order to determine the suitable technique for drug estimation, which would be employed in further research. Furthermore, comparative pharmacokinetic profile of the drug from lipid architectonics and drug suspension would be obtained post oral administration. Method: Lipid Architectonics (LA) of EVR was formulated using probe sonication technique and optimized using QbD (Box-Behnken design). For the estimation of drug during further analysis HPLC method has been validation on the parameters (Linearity, Precision, Accuracy, Robustness) and Limit of Detection (LOD) and Limit of Quantification (LOQ) has been determined. Furthermore, HPLC quantification of forced degradation studies was carried out under different stress conditions (acid induced, base induced, oxidative, photolytic and thermal). For pharmacokinetic (PK) study, Albino Wistar rats were used weighing between 200-250g. Different formulations were given per oral route, and blood was collected at designated time intervals. A plasma concentration profile over time was plotted from which the following parameters were determined: <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=AIDS" title="AIDS">AIDS</a>, <a href="https://publications.waset.org/abstracts/search?q=Elvitegravir" title=" Elvitegravir"> Elvitegravir</a>, <a href="https://publications.waset.org/abstracts/search?q=HPLC" title=" HPLC"> HPLC</a>, <a href="https://publications.waset.org/abstracts/search?q=nanostructured%20lipid%20carriers" title=" nanostructured lipid carriers"> nanostructured lipid carriers</a>, <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title=" pharmacokinetics"> pharmacokinetics</a> </p> <a href="https://publications.waset.org/abstracts/115553/development-of-lipid-architectonics-for-improving-efficacy-and-ameliorating-the-oral-bioavailability-of-elvitegravir" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/115553.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">138</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">32</span> Disposition Kinetics of Ciprofloxacin after Intramuscular Administration in Lohi Sheep</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Zahid%20Iqbal">Zahid Iqbal</a>, <a href="https://publications.waset.org/abstracts/search?q=Ijaz%20Javed"> Ijaz Javed</a>, <a href="https://publications.waset.org/abstracts/search?q=Riaz%20Hussain"> Riaz Hussain</a>, <a href="https://publications.waset.org/abstracts/search?q=Ibadullah%20Jan"> Ibadullah Jan</a>, <a href="https://publications.waset.org/abstracts/search?q=Amir%20Ali%20Khan"> Amir Ali Khan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> This study was conducted to investigate the disposition kinetics of ciprofloxacin and calculate its optimal dosage in Pakistani sheep of Lohi breed. Injectable preparation of ciprofloxacin was given intramuscularly to eight sheep at a dose of 5 mg/Kg. Before administration of drug blood sample was drawn from each animal. Post drug administration, blood samples were also drawn at various predetermined time periods. Drug concentration in the blood samples was assessed through high performance liquid chromatograph (HPLC). Data were best described by two compartment open model and different pharmacokinetic (PK) parameters were calculated. Cmax of 1.97 ± 0.15 µg/ml was reached at Tmax of 0.88 ± 0.09 hours. Half life of absorption (t1/2 abs) was observed to be 0.63 ± 0.16 hours while t1/2 α (distribution half life) and t1/2 ß (elimination half life) were found to be 0.46 ± 0.05 and 2.93 ± 0.45 hours, respectively. Vd (apparent volume of distribution) was calculated as 2.89 ± 0.30 L/kg while AUC (area under the curve) was 7.19 ± 0.38 µg.hr/mL and CL (total body clearance) was 0.75 ± 0.04 L/hr/kg. Using these parameters, an optimal intramuscular dosage of ciprofloxacin in adult Lohi sheep was calculated as 21.43 mg/kg, advised to be repeated after 24 hours. From this, we came to the conclusion that calculated dose was much higher than the dose advised by the foreign manufacturer and to avoid antimicrobial resistance, it is advised that this locally investigated dosage regimen should be strictly followed in local sheep. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=pharmacokinetics" title="pharmacokinetics">pharmacokinetics</a>, <a href="https://publications.waset.org/abstracts/search?q=dosage%20regimen" title=" dosage regimen"> dosage regimen</a>, <a href="https://publications.waset.org/abstracts/search?q=ciprofloxacin" title=" ciprofloxacin"> ciprofloxacin</a>, <a href="https://publications.waset.org/abstracts/search?q=HPLC" title=" HPLC"> HPLC</a>, <a href="https://publications.waset.org/abstracts/search?q=sheep" title=" sheep"> sheep</a> </p> <a href="https://publications.waset.org/abstracts/36585/disposition-kinetics-of-ciprofloxacin-after-intramuscular-administration-in-lohi-sheep" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/36585.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">539</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">31</span> Pharmacokinetic Study of Clarithromycin in Human Female of Pakistani Population</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Atifa%20Mushtaq">Atifa Mushtaq</a>, <a href="https://publications.waset.org/abstracts/search?q=Tanweer%20Khaliq"> Tanweer Khaliq</a>, <a href="https://publications.waset.org/abstracts/search?q=Hafiz%20Alam%20Sher"> Hafiz Alam Sher</a>, <a href="https://publications.waset.org/abstracts/search?q=Asia%20Farid"> Asia Farid</a>, <a href="https://publications.waset.org/abstracts/search?q=Anila%20Kanwal"> Anila Kanwal</a>, <a href="https://publications.waset.org/abstracts/search?q=Maliha%20Sarfraz"> Maliha Sarfraz</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The study was designed to assess the various pharmacokinetic parameters of a commercially available clarithromycin Tablet (Klaricid® 250 mg Abbot, Pakistan) in plasma sample of healthy adult female volunteers by applying a rapid, sensitive and accurate HPLC-UV analytical method. The human plasma samples were evaluated by using an isocratic High Performance Liquid Chromatography (HPLC) system of Sykam consisted of a pump with a column C18 column (250×4.6mn, 5µm) UV-detector. The mobile phase comprises of potassium dihydrogen phosphate (50 mM, pH 6.8, contained 0.7% triethylamine), methanol and acetonitrile (30:25:45, v/v/v) was delivered with injection volume of 20µL at flow rate of 1 mL/min. The detection was performed at λmax 275 nm. By applying this method, important pharmacokinetic parameters Cmax, Tmax, Area under curve (AUC), half-life (t1/2), , Volume of distribution (Vd) and Clearance (Cl) were measured. The parameters of pharmacokinetics of clarithromycin were calculated by software (APO) pharmacological analysis. Maximum plasma concentrations Cmax 2.78 ±0.33 µg/ml, time to reach maximum concentration tmax 2.82 ± 0.11 h and Area under curve AUC was 20.14 h.µg/ml. The mean ± SD values obtained for the pharmacokinetic parameters showed a significant difference in pharmacokinetic parameters observed in previous literature which emphasizes the need for dose adjustment of clarithromycin in Pakistani population. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=Pharmacokinetc" title="Pharmacokinetc">Pharmacokinetc</a>, <a href="https://publications.waset.org/abstracts/search?q=Clarothromycin" title="Clarothromycin">Clarothromycin</a>, <a href="https://publications.waset.org/abstracts/search?q=HPLC" title="HPLC">HPLC</a>, <a href="https://publications.waset.org/abstracts/search?q=Pakistan" title="Pakistan">Pakistan</a> </p> <a href="https://publications.waset.org/abstracts/143201/pharmacokinetic-study-of-clarithromycin-in-human-female-of-pakistani-population" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/143201.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">108</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">30</span> Preparation of Pegylated Interferon Alpha-2b with High Antiviral Activity Using Linear 20 KDa Polyethylene Glycol Derivative</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ehab%20El-Dabaa">Ehab El-Dabaa</a>, <a href="https://publications.waset.org/abstracts/search?q=Omnia%20Ali"> Omnia Ali</a>, <a href="https://publications.waset.org/abstracts/search?q=Mohamed%20Abd%20El-Hady"> Mohamed Abd El-Hady</a>, <a href="https://publications.waset.org/abstracts/search?q=Ahmed%20Osman"> Ahmed Osman</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Recombinant human interferon alpha 2 (rhIFN-α2) is FDA approved for treatment of some viral and malignant diseases. Approved pegylated rhIFN-α2 drugs have highly improved pharmacokinetics, pharmacodynamics and therapeutic efficiency compared to native protein. In this work, we studied the pegylation of purified properly refolded rhIFN-α2b using linear 20kDa PEG-NHS (polyethylene glycol- N-hydroxysuccinimidyl ester) to prepare pegylated rhIFN-α2b with high stability and activity. The effect of different parameters like rhIFN-α2b final concentration, pH, rhIFN-α2b/PEG molar ratios and reaction time on the efficiency of pegylation (high percentage of monopegylated rhIFN-α2b) have been studied in small scale (100µl) pegylation reaction trials. Study of the percentages of different components of these reactions (mono, di, polypegylated rhIFN-α2b and unpegylated rhIFN-α2b) indicated that 2h is optimum time to complete the reaction. The pegylation efficiency increased at pH 8 (57.9%) by reducing the protein concentration to 1mg/ml and reducing the rhIFN-α2b/PEG ratio to 1:2. Using larger scale pegylation reaction (65% pegylation efficiency), ion exchange chromatography method has been optimized to prepare and purify the monopegylated rhIFN-α2b with high purity (96%). The prepared monopegylated rhIFN-α2b had apparent Mwt of approximately 65 kDa and high in vitro antiviral activity (2.1x10⁷ ± 0.8 x10⁷ IU/mg). Although it retained approximately 8.4 % of the antiviral activity of the unpegylated rhIFN-α2b, its activity is high compared to other pegylated rhIFN-α2 developed by using similar approach or higher molecular weight branched PEG. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=antiviral%20activity" title="antiviral activity">antiviral activity</a>, <a href="https://publications.waset.org/abstracts/search?q=rhIFN-%CE%B12b" title=" rhIFN-α2b"> rhIFN-α2b</a>, <a href="https://publications.waset.org/abstracts/search?q=pegylation" title=" pegylation"> pegylation</a>, <a href="https://publications.waset.org/abstracts/search?q=pegylation%20efficiency" title=" pegylation efficiency"> pegylation efficiency</a> </p> <a href="https://publications.waset.org/abstracts/82826/preparation-of-pegylated-interferon-alpha-2b-with-high-antiviral-activity-using-linear-20-kda-polyethylene-glycol-derivative" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/82826.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">177</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">29</span> Potential Drug-Drug Interactions at a Referral Hematology-Oncology Ward in Iran: A Cross-Sectional Study</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Sara%20Ataei">Sara Ataei</a>, <a href="https://publications.waset.org/abstracts/search?q=Molouk%20Hadjibabaie"> Molouk Hadjibabaie</a>, <a href="https://publications.waset.org/abstracts/search?q=Shirinsadat%20Badri"> Shirinsadat Badri</a>, <a href="https://publications.waset.org/abstracts/search?q=Amirhossein%20Moslehi"> Amirhossein Moslehi</a>, <a href="https://publications.waset.org/abstracts/search?q=Iman%20Karimzadeh"> Iman Karimzadeh</a>, <a href="https://publications.waset.org/abstracts/search?q=Ardeshir%20Ghavamzadeh"> Ardeshir Ghavamzadeh </a> </p> <p class="card-text"><strong>Abstract:</strong></p> Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=drug%E2%80%93drug%20interactions" title="drug–drug interactions">drug–drug interactions</a>, <a href="https://publications.waset.org/abstracts/search?q=hematology%E2%80%93oncology%20ward" title=" hematology–oncology ward"> hematology–oncology ward</a>, <a href="https://publications.waset.org/abstracts/search?q=hematological%20malignancies" title=" hematological malignancies "> hematological malignancies </a> </p> <a href="https://publications.waset.org/abstracts/17983/potential-drug-drug-interactions-at-a-referral-hematology-oncology-ward-in-iran-a-cross-sectional-study" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/17983.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">453</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">28</span> Network Pharmacological Evaluation of Holy Basil Bioactive Phytochemicals for Identifying Novel Potential Inhibitors Against Neurodegenerative Disorder</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Bhuvanesh%20Baniya">Bhuvanesh Baniya</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=holy%20basil" title="holy basil">holy basil</a>, <a href="https://publications.waset.org/abstracts/search?q=network%20pharmacology" title=" network pharmacology"> network pharmacology</a>, <a href="https://publications.waset.org/abstracts/search?q=neurodegeneration" title=" neurodegeneration"> neurodegeneration</a>, <a href="https://publications.waset.org/abstracts/search?q=active%20phytochemicals" title=" active phytochemicals"> active phytochemicals</a>, <a href="https://publications.waset.org/abstracts/search?q=molecular%20docking%20and%20simulation" title=" molecular docking and simulation"> molecular docking and simulation</a> </p> <a href="https://publications.waset.org/abstracts/162002/network-pharmacological-evaluation-of-holy-basil-bioactive-phytochemicals-for-identifying-novel-potential-inhibitors-against-neurodegenerative-disorder" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/162002.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">100</span> </span> </div> </div> <ul class="pagination"> <li class="page-item disabled"><span class="page-link">&lsaquo;</span></li> <li class="page-item active"><span class="page-link">1</span></li> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=pharmacokinetics&page=2">2</a></li> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=pharmacokinetics&page=2" rel="next">&rsaquo;</a></li> </ul> </div> </main> <footer> <div 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