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pharmacokinetics</title> <meta name="description" content="Search results for: isoniazid pharmacokinetics"> <meta name="keywords" content="isoniazid 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 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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="isoniazid 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> 82</div> </div> </div> </div> <h1 class="mt-3 mb-3 text-center" style="font-size:1.6rem;">Search results for: isoniazid pharmacokinetics</h1> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">82</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">81</span> Erythema Multiforme Exudativum Major Caused by Isoniazid Hypersensitivity in a Child</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Azwin%20Lubis">Azwin Lubis</a>, <a href="https://publications.waset.org/abstracts/search?q=Rika%20Hapsari"> Rika Hapsari</a>, <a href="https://publications.waset.org/abstracts/search?q=Zahrah%20Hikmah"> Zahrah Hikmah</a>, <a href="https://publications.waset.org/abstracts/search?q=Anang%20Endaryanto"> Anang Endaryanto</a>, <a href="https://publications.waset.org/abstracts/search?q=Ariyanto%20Harsono"> Ariyanto Harsono</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=erythema%20multiforme%20exudativum%20major" title="erythema multiforme exudativum major">erythema multiforme exudativum major</a>, <a href="https://publications.waset.org/abstracts/search?q=hypersensitivity" title=" hypersensitivity"> hypersensitivity</a>, <a href="https://publications.waset.org/abstracts/search?q=elimination%20test" title=" elimination test"> elimination test</a>, <a href="https://publications.waset.org/abstracts/search?q=provocation%20test" title=" provocation test"> provocation test</a> </p> <a href="https://publications.waset.org/abstracts/61126/erythema-multiforme-exudativum-major-caused-by-isoniazid-hypersensitivity-in-a-child" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/61126.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">249</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">80</span> Evaluation of the Microscopic-Observation Drug-Susceptibility Assay Drugs Concentration for Detection of Multidrug-Resistant Tuberculosis</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Anita">Anita</a>, <a href="https://publications.waset.org/abstracts/search?q=Sari%20Septiani%20Tangke"> Sari Septiani Tangke</a>, <a href="https://publications.waset.org/abstracts/search?q=Rusdina%20Bte%20Ladju"> Rusdina Bte Ladju</a>, <a href="https://publications.waset.org/abstracts/search?q=Nasrum%20Massi"> Nasrum Massi</a> </p> <p class="card-text"><strong>Abstract:</strong></p> New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=isoniazid" title="isoniazid">isoniazid</a>, <a href="https://publications.waset.org/abstracts/search?q=MODS%20assay" title=" MODS assay"> MODS assay</a>, <a href="https://publications.waset.org/abstracts/search?q=MDR-TB" title=" MDR-TB"> MDR-TB</a>, <a href="https://publications.waset.org/abstracts/search?q=rifampin" title=" rifampin "> rifampin </a> </p> <a href="https://publications.waset.org/abstracts/8582/evaluation-of-the-microscopic-observation-drug-susceptibility-assay-drugs-concentration-for-detection-of-multidrug-resistant-tuberculosis" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/8582.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">320</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">79</span> Mutations in rpoB, katG and inhA Genes: The Association with Resistance to Rifampicin and Isoniazid in Egyptian Mycobacterium tuberculosis Clinical Isolates</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ayman%20K.%20El%20Essawy">Ayman K. El Essawy</a>, <a href="https://publications.waset.org/abstracts/search?q=Amal%20M.%20Hosny"> Amal M. Hosny</a>, <a href="https://publications.waset.org/abstracts/search?q=Hala%20M.%20Abu%20Shady"> Hala M. Abu Shady</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=M.%20tuberculosis" title="M. tuberculosis">M. tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=rpoB" title=" rpoB"> rpoB</a>, <a href="https://publications.waset.org/abstracts/search?q=KatG" title=" KatG"> KatG</a>, <a href="https://publications.waset.org/abstracts/search?q=inhA" title=" inhA"> inhA</a>, <a href="https://publications.waset.org/abstracts/search?q=genotype%20MTBDRplus" title=" genotype MTBDRplus"> genotype MTBDRplus</a> </p> <a href="https://publications.waset.org/abstracts/115843/mutations-in-rpob-katg-and-inha-genes-the-association-with-resistance-to-rifampicin-and-isoniazid-in-egyptian-mycobacterium-tuberculosis-clinical-isolates" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/115843.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">166</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">78</span> Investigation of Rifampicin and Isoniazid Resistance Mutated Genes in Mycobacterium Tuberculosis Isolated From Patients</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Seyyed%20Mohammad%20Amin%20Mousavi%20Sagharchi">Seyyed Mohammad Amin Mousavi Sagharchi</a>, <a href="https://publications.waset.org/abstracts/search?q=Alireza%20Mahmoudi%20Nasab"> Alireza Mahmoudi Nasab</a>, <a href="https://publications.waset.org/abstracts/search?q=Tim%20Bakker"> Tim Bakker</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Introduction: Mycobacterium tuberculosis (MTB) is the most intelligent bacterium that existed in the world to our best knowledge. This bacterium can cause tuberculosis (TB) which is responsible for its spread speed and murder of millions of people around the world. MTB has the practical function to escape from anti-tuberculosis drugs (AT), for this purpose, it handles some mutations in the main genes and creates new patterns for inhibited genes. Method and materials: Researchers have their best tries to safely isolate MTB from the sputum specimens of 35 patients in some hospitals in the Tehran province and detect MTB by culture on Löwenstein-Jensen (LJ) medium and microscopic examination. DNA was extracted from the established bacterial colony by enzymatic extraction method. It was amplified by the polymerase chain reaction (PCR) method, reverse hybridization, and evaluation for detection of resistance genes; generally, researchers apply GenoType MTBDRplus assay. Results: Investigations of results declare us that 21 of the isolated specimens (about 60%) have mutation in rpoB gene, which resisted to rifampicin (most prevalence), and 8 of them (about 22.8%) have mutation in katG or inhA genes which resisted to isoniazid. Also, 4 of them (about 11.4%) don't have any mutation, and 2 of them (about 5.7%) have mutation in every three genes, which makes them resistant to the two drugs mentioned above. Conclusion: Rifampicin and isoniazid are two essential AT that using in the first line of treatment. Resistance in rpoB, and katG, and inhA genes related to mentioned drugs lead to ineffective treatment. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=mycobacterium%20tuberculosis" title="mycobacterium tuberculosis">mycobacterium tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title=" tuberculosis"> tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20resistance" title=" drug resistance"> drug resistance</a>, <a href="https://publications.waset.org/abstracts/search?q=isoniazid" title=" isoniazid"> isoniazid</a>, <a href="https://publications.waset.org/abstracts/search?q=rifampicin" title=" rifampicin"> rifampicin</a> </p> <a href="https://publications.waset.org/abstracts/165030/investigation-of-rifampicin-and-isoniazid-resistance-mutated-genes-in-mycobacterium-tuberculosis-isolated-from-patients" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/165030.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">96</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">77</span> Role of Oxidative Stress and Nitric Oxide in the Protective Effects of Simvastatine against Isoniazid-Rifampicin-Induced Hepatotoxicity in Rats</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Mabroka%20Omar%20Sherehe">Mabroka Omar Sherehe</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Despite the great efficacy of isoniazid (INH) and rifampicine (RIF) combination in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of simvastatin (sim) against combination-induced hepatotoxicity was investigated in the present study. The administration of INH-RIF combination (50mg/kg each for 14 days) resulted in a significant increased activities of serum alanine and aspartate aminotransferases, such effects were further supported by histopathological studies. INH-RIF combination produced a significant increase in liver lipid, decreased SOD and CAT, and a significant depletion of GSH level. Additionally, treatment with INH-RIF combination resulted in a significant increase in liver MPO activity. The lipid-lowering drug, Sim demonstrated in the current study an evident antioxidant action, such effect was mediated via decreasing the elevated MDA, MPO, and restoring liver CAT activity. Additionally, Sim restored liver NO level to near basal value Furthermore, one cannot rule out the lipid-lowering effect of Sim that would probably add to its beneficial hepatoprotective antioxidant activity, where Sim decreased the elevated cholesterol, TGs and LDL cholesterol level and increased the serum HDL cholesterol level. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=isoniazid" title="isoniazid">isoniazid</a>, <a href="https://publications.waset.org/abstracts/search?q=rifampicine" title=" rifampicine"> rifampicine</a>, <a href="https://publications.waset.org/abstracts/search?q=oxidative%20stress" title=" oxidative stress"> oxidative stress</a>, <a href="https://publications.waset.org/abstracts/search?q=nitric%20oxide" title=" nitric oxide "> nitric oxide </a> </p> <a href="https://publications.waset.org/abstracts/19899/role-of-oxidative-stress-and-nitric-oxide-in-the-protective-effects-of-simvastatine-against-isoniazid-rifampicin-induced-hepatotoxicity-in-rats" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/19899.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">616</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">76</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">75</span> Docking and Dynamic Molecular Study of Isoniazid Derivatives as Anti-Tuberculosis Drug Candidate</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Richa%20Mardianingrum">Richa Mardianingrum</a>, <a href="https://publications.waset.org/abstracts/search?q=Srie%20R.%20N.%20Endah"> Srie R. N. Endah</a> </p> <p class="card-text"><strong>Abstract:</strong></p> In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=anti-tuberculosis" title="anti-tuberculosis">anti-tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=docking" title=" docking"> docking</a>, <a href="https://publications.waset.org/abstracts/search?q=Inhibin%20alpha%20subunit" title=" Inhibin alpha subunit"> Inhibin alpha subunit</a>, <a href="https://publications.waset.org/abstracts/search?q=InhA" title=" InhA"> InhA</a>, <a href="https://publications.waset.org/abstracts/search?q=inhibition" title=" inhibition"> inhibition</a>, <a href="https://publications.waset.org/abstracts/search?q=synthesis" title=" synthesis"> synthesis</a>, <a href="https://publications.waset.org/abstracts/search?q=isonicotinohydrazide" title=" isonicotinohydrazide"> isonicotinohydrazide</a> </p> <a href="https://publications.waset.org/abstracts/92270/docking-and-dynamic-molecular-study-of-isoniazid-derivatives-as-anti-tuberculosis-drug-candidate" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/92270.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">181</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">74</span> In silico Analysis of Isoniazid Resistance in Mycobacterium tuberculosis</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=A.%20Nusrath%20Unissa">A. Nusrath Unissa</a>, <a href="https://publications.waset.org/abstracts/search?q=Sameer%20Hassan"> Sameer Hassan</a>, <a href="https://publications.waset.org/abstracts/search?q=Luke%20Elizabeth%20Hanna"> Luke Elizabeth Hanna</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=Mycobacterium%20tuberculosis" title="Mycobacterium tuberculosis">Mycobacterium tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=KatG" title=" KatG"> KatG</a>, <a href="https://publications.waset.org/abstracts/search?q=INH%20resistance" title=" INH resistance"> INH resistance</a>, <a href="https://publications.waset.org/abstracts/search?q=mutants" title=" mutants"> mutants</a>, <a href="https://publications.waset.org/abstracts/search?q=modelling" title=" modelling"> modelling</a>, <a href="https://publications.waset.org/abstracts/search?q=docking" title=" docking"> docking</a> </p> <a href="https://publications.waset.org/abstracts/6727/in-silico-analysis-of-isoniazid-resistance-in-mycobacterium-tuberculosis" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/6727.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">317</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">73</span> Efficiency of Treatment in Patients with Newly Diagnosed Destructive Pulmonary Tuberculosis Using Intravenous Chemotherapy</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=M.%20Kuzhko">M. Kuzhko</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Gumeniuk"> M. Gumeniuk</a>, <a href="https://publications.waset.org/abstracts/search?q=D.%20Butov"> D. Butov</a>, <a href="https://publications.waset.org/abstracts/search?q=T.%20Tlustova"> T. Tlustova</a>, <a href="https://publications.waset.org/abstracts/search?q=O.%20Denysov"> O. Denysov</a>, <a href="https://publications.waset.org/abstracts/search?q=T.%20Sprynsian"> T. Sprynsian</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: The aim of the research was to determine the effectiveness of chemotherapy using intravenous antituberculosis drugs compared with their oral administration during the intensive phase of treatment. Methods: 152 tuberculosis patients were randomized into 2 groups: Main (n=65) who received isoniazid, ethambutol and sodium rifamycin intravenous + pyrazinamide per os and control (n=87) who received all the drugs (isoniazid, rifampicin, ethambutol, pyrazinamide) orally. Results: After 2 weeks of treatment symptoms of intoxication disappeared in 59 (90.7±3.59 %) of patients of the main group and 60 (68.9±4.9 %) patients in the control group, p<0.05. The mean duration of symptoms of intoxication in patients main group was 9.6±0.7 days, in control group – 13.7±0.9 days. After completing intensive phase sputum conversion was found in all the patients main group and 71 (81.6±4.1 %) patients control group p < 0.05. The average time of sputum conversion in main group was 1.6±0.1 months and 1.9±0.1 months in control group, p > 0.05. In patients with destructive pulmonary tuberculosis time to sputum conversion was 1.7±0.1 months in main group and 2.2±0.2 months in control group, p < 0.05. The average time of cavities healing in main group was 2.9±0.2 months and 3.9±0.2 months in the control group, p < 0.05. Conclusions: In patients with newly diagnosed destructive pulmonary tuberculosis use of isoniazid, ethambutol and sodium rifamycin intravenous in the intensive phase of chemotherapy resulted in a significant reduction in terms of the disappearance of symptoms of intoxication and sputum conversion. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=intravenous%20chemotherapy" title="intravenous chemotherapy">intravenous chemotherapy</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title=" tuberculosis"> tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=treatment%20efficiency" title=" treatment efficiency"> treatment efficiency</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis%20drugs" title=" tuberculosis drugs"> tuberculosis drugs</a> </p> <a href="https://publications.waset.org/abstracts/61715/efficiency-of-treatment-in-patients-with-newly-diagnosed-destructive-pulmonary-tuberculosis-using-intravenous-chemotherapy" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/61715.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">202</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">72</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">71</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">611</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">70</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">69</span> Drug Susceptibility and Genotypic Assessment of Mycobacterial Isolates from Pulmonary Tuberculosis Patients in North East Ethiopia</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Minwuyelet%20Maru">Minwuyelet Maru</a>, <a href="https://publications.waset.org/abstracts/search?q=Solomon%20Habtemariam"> Solomon Habtemariam</a>, <a href="https://publications.waset.org/abstracts/search?q=Endalamaw%20Gadissa"> Endalamaw Gadissa</a>, <a href="https://publications.waset.org/abstracts/search?q=Abraham%20Aseffa"> Abraham Aseffa</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: Tuberculosis is a major public health problem in Ethiopia. The burden of TB is aggravated by emergence and expansion of drug resistant tuberculosis and different lineages of Mycobacterium tuberculosis (M. tuberculosis) have been reported in many parts of the country. Describing strains of Mycobacterial isolates and drug susceptibility pattern is necessary. Method: Sputum samples were collected from smear positive pulmonary TB patients age >= 7 years between October 1, 2012 to September 30, 2013 and Mycobacterial strains isolated on Loweensten Jensen (LJ) media. Each strain was characterized by deletion typing and Spoligotyping. Drug sensitivity testing was determined with the indirect proportion method using Middle brook 7H10 media and association to determine possible risk factors to drug resistance was done. Result: A total of 144 smear positive pulmonary tuberculosis patients were enrolled. The age of participants ranged from 7 to 78 with mean age of 29.22 (±10.77) years. In this study 82.2% (n=97) of the isolates were sensitive to the four first line anti-tuberculosis drugs and resistance to any of the four drugs tested was 17.8% (n=21). A high frequency of any resistance was observed in isoniazid, 13.6%, (n=16) followed by streptomycin, 11.8% (n=14). No significant association of isoniazid resistance with HIV, sex and history of previous TB treatment was observed but there was significant association with age, high between 31-35 years of age (p=0.01). Majority, 89.9% (n=128) of participants were new cases and only 11.1% (n=16) had history of previous TB treatment. No MDR-TB from new cases and 2 MDRTB (13.3%) was isolated from re-treatment cases which was significantly associated with previous TB treatment (p<0.01). Thirty two different types of spoligotype patterns were identified and 74.1% were grouped in to 13 clusters. The dominant strains were SIT 25, 18.1% (n=21), SIT 53, 17.2% (n=20) and SIT 149, 8.6% (n=10). Lineage 4 is the predominant lineage followed by lineage 3 and lineage 7 comprising 65.5% (n=76), 28.4% (n=33) and 6% (n=7) respectively. Majority of strains from lineage 3 and 4 were SIT 25 (63.6%) and SIT 53 (26.3%) whereas SIT 343 was the dominant strain from lineage 7 (71.4%). Conclusion: Wide spread of lineage 3 and lineage 4 of the modern lineage and high number of strain cluster indicates high ongoing transmission. The high proportion resistance to any of the first line anti-tuberculosis drugs may be a potential source in the emergence of MDR-TB. Wide spread of SIT 25 and SIT 53 having a tendency of ease transmission and presence of higher resistance of isoniazid in working and mobile age group, 31-35 years of age may increase risk of drug resistant strains transmission. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title="tuberculosis">tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=drug%20susceptibility" title=" drug susceptibility"> drug susceptibility</a>, <a href="https://publications.waset.org/abstracts/search?q=strain%20diversity" title=" strain diversity"> strain diversity</a>, <a href="https://publications.waset.org/abstracts/search?q=lineage" title=" lineage"> lineage</a>, <a href="https://publications.waset.org/abstracts/search?q=Ethiopia" title=" Ethiopia"> Ethiopia</a>, <a href="https://publications.waset.org/abstracts/search?q=spoligotyping" title=" spoligotyping "> spoligotyping </a> </p> <a href="https://publications.waset.org/abstracts/8015/drug-susceptibility-and-genotypic-assessment-of-mycobacterial-isolates-from-pulmonary-tuberculosis-patients-in-north-east-ethiopia" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/8015.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">375</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">68</span> Synthesis, Characterization, Theoretical Crystal Structures and Antitubercular Activity Study of (E)-N'-(2,4-Dihydroxybenzylidene) Nicotinohydrazide and Some of Its Metal Complexes</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Ogunniran%20Kehinde%20Olurotimi">Ogunniran Kehinde Olurotimi</a>, <a href="https://publications.waset.org/abstracts/search?q=Adekoya%20Joseph"> Adekoya Joseph</a>, <a href="https://publications.waset.org/abstracts/search?q=Ehi-Eromosele%20Cyril"> Ehi-Eromosele Cyril</a>, <a href="https://publications.waset.org/abstracts/search?q=Mehdi%20Shihab"> Mehdi Shihab</a>, <a href="https://publications.waset.org/abstracts/search?q=Mesubi%20Adediran"> Mesubi Adediran</a>, <a href="https://publications.waset.org/abstracts/search?q=Tadigoppula%20Narender"> Tadigoppula Narender</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Nicotinic acid hydrazide and 2,4-dihydoxylbenzaldehyde were condensed at 20°C to form an acylhydrazone (H3L) with ONO coordination pattern. The structure of the acylhydrazone was elucidated by using CHN analyzer, ESI mass spectrometry, IR, 1H NMR, 13C NMR and 2D NMR such as COSY and HSQC. Thereafter, five novel metal complexes [Mn(II), Fe(II), Pt(II) Zn(II) and Pd(II)] of the hydrazone ligand were synthesized and their structural characterization were achieved by several physicochemical methods, namely elemental analysis, electronic spectra, infrared, EPR, molar conductivity and powder X-ray diffraction studies. Structural geometries of some of the compounds were supported by using Hyper Chem-8 program for the molecular mechanics and semi-empirical calculations. The stability energy (E) and electron potentials (eV) for the frontier molecules were calculated by using PM3 method. An octahedral geometry was suggested for both Pd(II) and Zn(II) complexes while both Mn(II) and Fe(II) complexes conformed with tetrahedral pyramidal. However, Pt(II) complex agreed with tetrahedral geometry. In vitro antitubercular activity study of the ligand and the metal complexes were evaluated against Mycobacterium tuberculosis, H37Rv, by using micro-diluted method. The results obtained revealed that (PtL1) (MIC = 0.56 µg/mL), (ZnL1) (MIC = 0.61 µg/mL), (MnL1) (MIC = 0.71 µg/mL) and (FeL1) (MIC = 0.82 µg/mL), exhibited a significant activity when compared with first line drugs such as isoniazid (INH) (MIC = 0.9 µg/mL). H3L1 exhibited lesser antitubercular activity with MIC value of 1.02 µg/mL. However, the metal complexes displayed higher cytoxicity but were found to be non-significant different (P ˂ 0.05) to isoniazid drug. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=hydrazones" title="hydrazones">hydrazones</a>, <a href="https://publications.waset.org/abstracts/search?q=electron%20spin%20resonance" title=" electron spin resonance"> electron spin resonance</a>, <a href="https://publications.waset.org/abstracts/search?q=thermogravimetric" title=" thermogravimetric"> thermogravimetric</a>, <a href="https://publications.waset.org/abstracts/search?q=powder%20X-ray%20diffraction" title=" powder X-ray diffraction"> powder X-ray diffraction</a>, <a href="https://publications.waset.org/abstracts/search?q=antitubercular%20agents" title=" antitubercular agents"> antitubercular agents</a> </p> <a href="https://publications.waset.org/abstracts/45608/synthesis-characterization-theoretical-crystal-structures-and-antitubercular-activity-study-of-e-n-24-dihydroxybenzylidene-nicotinohydrazide-and-some-of-its-metal-complexes" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/45608.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">268</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">67</span> A Study of 3 Different Reintroduction Regimens in Anti-Tubercular Therapy-Induced Hepatitis in Extra-Pulmonary Tuberculosis</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Alpana%20Meena">Alpana Meena</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Background: Tuberculosis is one of the major causes of death in south-east nations. Anti-TB–induced hepatotoxicity (AIH) is associated with a mortality of 6%–12%. The risk is increased when the drugs are combined. Reintroduction of anti-tuberculosis drugs in patients with AIH has never been studied systematically. The present study was planned to see the clinical profile of patients of AIH and the response to reintroduction of therapy. Methods: The trial was conducted in the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, on 32 patients with extra-pulmonary tuberculosis who developed AIH. Patients were randomly allocated into 3 groups. In group 1- Isoniazid (INH) and Rifampicin (RIF) were given at full dosages (weight calculated) from day 1. In group 2- RIF was given at maximum dosage from day 1 and INH at maximum dosage from day 8. In group 3- INH was given at maximum dosage from day 1 and RIF at maximum dosage from day 8. Pyrazinamide was added when above regimens were tolerated. Results: The mean age of presentation was 29.37±13.497 years. The incidence was found to be highest in patients with tubercular meningitis (41%) followed by abdominal, pericardial, disseminated, spinal, and lymph nodes. The mean latent period for development of AIH was 7.84 days ± 6.149 days and the median normalization days for LFT’s was 8.81 ± 4.22 days (3-21). In the study, 21% patients had recurrence of AIH with majority of patients having tolerated the reintroduction of drugs. Pyrazinamide was introduced after establishing isoniazid and rifampicin safety, thus emphasizing the role of gradual reintroduction of ATT to avoid the combined effects of hepatotoxicity. Conclusion: To conclude, the recurrence rate of hepatotoxicity was not statistically significant between the three groups studied (p > 0.05), and thus all 3 hepatotoxic drugs can be reintroduced safely in patients developing AIH. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=anti-tubercular%20therapy%20induced%20hepatotoxicity" title="anti-tubercular therapy induced hepatotoxicity">anti-tubercular therapy induced hepatotoxicity</a>, <a href="https://publications.waset.org/abstracts/search?q=extra-pulmonary%20tuberculosis" title=" extra-pulmonary tuberculosis"> extra-pulmonary tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=reintroduction%20regimens" title=" reintroduction regimens"> reintroduction regimens</a>, <a href="https://publications.waset.org/abstracts/search?q=risk%20factors" title=" risk factors"> risk factors</a> </p> <a href="https://publications.waset.org/abstracts/38323/a-study-of-3-different-reintroduction-regimens-in-anti-tubercular-therapy-induced-hepatitis-in-extra-pulmonary-tuberculosis" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/38323.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">299</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">66</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">65</span> Human Beta Defensin 1 as Potential Antimycobacterial Agent against Active and Dormant Tubercle Bacilli</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Richa%20Sharma">Richa Sharma</a>, <a href="https://publications.waset.org/abstracts/search?q=Uma%20Nahar"> Uma Nahar</a>, <a href="https://publications.waset.org/abstracts/search?q=Sadhna%20Sharma"> Sadhna Sharma</a>, <a href="https://publications.waset.org/abstracts/search?q=Indu%20Verma"> Indu Verma</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Counteracting the deadly pathogen Mycobacterium tuberculosis (M. tb) effectively is still a global challenge. Scrutinizing alternative weapons like antimicrobial peptides to strengthen existing tuberculosis artillery is urgently required. Considering the antimycobacterial potential of Human Beta Defensin 1 (HBD-1) along with isoniazid, the present study was designed to explore the ability of HBD-1 to act against active and dormant M. tb. HBD-1 was screened in silico using antimicrobial peptide prediction servers to identify its short antimicrobial motif. The activity of both HBD-1 and its selected motif (Pep B) was determined at different concentrations against actively growing M. tb in vitro and ex vivo in monocyte derived macrophages (MDMs). Log phase M. tb was grown along with HBD-1 and Pep B for 7 days. M. tb infected MDMs were treated with HBD-1 and Pep B for 72 hours. Thereafter, colony forming unit (CFU) enumeration was performed to determine activity of both peptides against actively growing in vitro and intracellular M. tb. The dormant M. tb models were prepared by following two approaches and treated with different concentrations of HBD-1 and Pep B. Firstly, 20-22 days old M. tbH37Rv was grown in potassium deficient Sauton media for 35 days. The presence of dormant bacilli was confirmed by Nile red staining. Dormant bacilli were further treated with rifampicin, isoniazid, HBD-1 and its motif for 7 days. The effect of both peptides on latent bacilli was assessed by colony forming units (CFU) and most probable number (MPN) enumeration. Secondly, human PBMC granuloma model was prepared by infecting PBMCs seeded on collagen matrix with M. tb(MOI 0.1) for 10 days. Histopathology was done to confirm granuloma formation. The granuloma thus formed was incubated for 72 hours with rifampicin, HBD-1 and Pep B individually. Difference in bacillary load was determined by CFU enumeration. The minimum inhibitory concentrations of HBD-1 and Pep B restricting growth of mycobacteria in vitro were 2μg/ml and 20μg/ml respectively. The intracellular mycobacterial load was reduced significantly by HBD-1 and Pep B at 1μg/ml and 5μg/ml respectively. Nile red positive bacterial population, high MPN/ low CFU count and tolerance to isoniazid, confirmed the formation of potassium deficienybaseddormancy model. HBD-1 (8μg/ml) showed 96% and 99% killing and Pep B (40μg/ml) lowered dormant bacillary load by 68.89% and 92.49% based on CFU and MPN enumeration respectively. Further, H&E stained aggregates of macrophages and lymphocytes, acid fast bacilli surrounded by cellular aggregates and rifampicin resistance, indicated the formation of human granuloma dormancy model. HBD-1 (8μg/ml) led to 81.3% reduction in CFU whereas its motif Pep B (40μg/ml) showed only 54.66% decrease in bacterial load inside granuloma. Thus, the present study indicated that HBD-1 and its motif are effective antimicrobial players against both actively growing and dormant M. tb. They should be further explored to tap their potential to design a powerful weapon for combating tuberculosis. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=antimicrobial%20peptides" title="antimicrobial peptides">antimicrobial peptides</a>, <a href="https://publications.waset.org/abstracts/search?q=dormant" title=" dormant"> dormant</a>, <a href="https://publications.waset.org/abstracts/search?q=human%20beta%20defensin%201" title=" human beta defensin 1"> human beta defensin 1</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title=" tuberculosis"> tuberculosis</a> </p> <a href="https://publications.waset.org/abstracts/59525/human-beta-defensin-1-as-potential-antimycobacterial-agent-against-active-and-dormant-tubercle-bacilli" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/59525.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">263</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">64</span> Scale up of Isoniazid Preventive Therapy: A Quality Management Approach in Nairobi County, Kenya</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=E.%20Omanya">E. Omanya</a>, <a href="https://publications.waset.org/abstracts/search?q=E.%20Mueni"> E. Mueni</a>, <a href="https://publications.waset.org/abstracts/search?q=G.%20Makau"> G. Makau</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Kariuki"> M. Kariuki</a> </p> <p class="card-text"><strong>Abstract:</strong></p> HIV infection is the strongest risk factor for a person to develop TB. Isoniazid preventive therapy (IPT) for People Living with HIV (PLWHIV) not only reduces the individual patients’ risk of developing active TB but mitigates cross infection. In Kenya, IPT for six months was recommended through the National TB, Leprosy and Lung Disease Program to treat latent TB. In spite of this recommendation by the national government, uptake of IPT among PLHIV remained low in Kenya by the end of 2015. The USAID/Kenya and East Africa Afya Jijini project, which supports 42 TBHIV health facilities in Nairobi County, began addressing low uptake of IPT through Quality Improvement (QI) teams set up at the facility level. Quality is characterized by WHO as one of the four main connectors between health systems building blocks and health systems outputs. Afya Jijini implements the Kenya Quality Model for Health, which involves QI teams being formed at the county, sub-county and facility levels. The teams review facility performance to identify gaps in service delivery and use QI tools to monitor and improve performance. Afya Jijini supported the formation of these teams in 42 facilities and built the teams’ capacity to review data and use QI principles to identify and address performance gaps. When the QI teams began working on improving IPT uptake among PLHIV, uptake was at 31.8%. The teams first conducted a root cause analysis using cause and effect diagrams, which help the teams to brainstorm on and to identify barriers to IPT uptake among PLHIV at the facility level. This is a participatory process where program staff provides technical support to the QI teams in problem identification and problem-solving. The gaps identified were inadequate knowledge and skills on the use of IPT among health care workers, lack of awareness of IPT by patients, inadequate monitoring and evaluation tools, and poor quantification and forecasting of IPT commodities. In response, Afya Jijini trained over 300 health care workers on the administration of IPT, supported patient education, supported quantification and forecasting of IPT commodities, and provided IPT data collection tools to help facilities monitor their performance. The facility QI teams conducted monthly meetings to monitor progress on implementation of IPT and took corrective action when necessary. IPT uptake improved from 31.8% to 61.2% during the second year of the Afya Jijini project and improved to 80.1% during the third year of the project’s support. Use of QI teams and root cause analysis to identify and address service delivery gaps, in addition to targeted program interventions and continual performance reviews, can be successful in increasing TB related service delivery uptake at health facilities. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=isoniazid" title="isoniazid">isoniazid</a>, <a href="https://publications.waset.org/abstracts/search?q=quality" title=" quality"> quality</a>, <a href="https://publications.waset.org/abstracts/search?q=health%20care%20workers" title=" health care workers"> health care workers</a>, <a href="https://publications.waset.org/abstracts/search?q=people%20leaving%20with%20HIV" title=" people leaving with HIV"> people leaving with HIV</a> </p> <a href="https://publications.waset.org/abstracts/106750/scale-up-of-isoniazid-preventive-therapy-a-quality-management-approach-in-nairobi-county-kenya" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/106750.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">99</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">63</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">62</span> Efficacy and Safety of Inhaled Nebulized Chemotherapy in Treatment of Patients with Newly Diagnosed Pulmonary Tuberculosis in Comparison to Standard Antimycobacterial Therapy</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=M.%20Kuzhko">M. Kuzhko</a>, <a href="https://publications.waset.org/abstracts/search?q=M.%20Gumeniuk"> M. Gumeniuk</a>, <a href="https://publications.waset.org/abstracts/search?q=D.%20Butov"> D. Butov</a>, <a href="https://publications.waset.org/abstracts/search?q=T.%20Tlustova"> T. Tlustova</a>, <a href="https://publications.waset.org/abstracts/search?q=O.%20Denysov"> O. Denysov</a>, <a href="https://publications.waset.org/abstracts/search?q=T.%20Sprynsian"> T. Sprynsian</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Abstract: The objective of this work was to study the efficacy and safety of inhaled nebulized chemotherapy in the treatment of patients with newly diagnosed pulmonary tuberculosis in comparison with standard antimycobacterial therapy. Materials and methods: The study involved 68 patients aged between 20 and 70 years with newly diagnosed pulmonary tuberculosis. Patients were allocated to two groups. The first (main, n=21) group of patients received standard chemotherapy and further 0.15 g of isoniazid and rifampicin 0.15 g inhaled through a nebulizer, also they received salmeterol 50 mcg + fluticasone propionate 250 mcg at 2 breaths twice a day for 2 months. The second (control, n=47) group of patients received standard chemotherapy, consisting of orally administered isoniazid (0.3 g), rifampicin (0.6 g), pyrazinamide (2 g), ethambutol (1.2 g) with a dose reduction after the intensive phase of the therapy. The anti-TB drugs were procured through the Ukraine’s centralized national supply system. Results: Intoxication symptoms in the first group reduced following 1.39±0.18 months, whereas in the second group, intoxication symptoms reduced following 2.7±0.1 months, p<.001. Moreover, respiratory symptoms regression in the first group was observed following 1.6±0.2 months, whereas in the second group – following 2.5±0.2 months, p<0.05. Bacillary excretion period evaluated within 1 month was reduced, as it was shown by 66.6±10.5% in the main group compared to 27.6±6.5%, p<0.05, in the control group. In addition, period of cavities healing was reduced to 2.9±0.2 months in the main group compared to 3.7±0.1 months, p<0.05, in the control group. Residual radiological lung damage findings (large residual changes) were observed in 22 (23.8±9.5 %) patients of the main group versus 24 (51.0±7.2 %) patients in the control group, p<0.05. After completion of treatment scar stenosis of the bronchi II-III art. diagnosed in 3 (14.2±7.8%) patients in main group and 17 (68.0±6.8%) - control group, p<0.05. The duration of hospital treatment was 2.4±0.4 months in main group and 4.1±0.4 months in control group, p<0.05. Conclusion: Administration of of inhaled nebulized chemotherapy in patients with newly diagnosed pulmonary tuberculosis resulted in a comparatively quick reduction of disease manifestation. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=inhaled%20nebulized%20chemotherapy" title="inhaled nebulized chemotherapy">inhaled nebulized chemotherapy</a>, <a href="https://publications.waset.org/abstracts/search?q=pulmonary%20tuberculosis" title=" pulmonary tuberculosis"> pulmonary tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title=" tuberculosis"> tuberculosis</a>, <a href="https://publications.waset.org/abstracts/search?q=treatment%20of%20tuberculosis" title=" treatment of tuberculosis"> treatment of tuberculosis</a> </p> <a href="https://publications.waset.org/abstracts/61666/efficacy-and-safety-of-inhaled-nebulized-chemotherapy-in-treatment-of-patients-with-newly-diagnosed-pulmonary-tuberculosis-in-comparison-to-standard-antimycobacterial-therapy" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/61666.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">197</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">61</span> Iron-Metal-Organic Frameworks: Potential Application as Theranostics for Inhalable Therapy of Tuberculosis</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Gabriela%20Wyszogrodzka">Gabriela Wyszogrodzka</a>, <a href="https://publications.waset.org/abstracts/search?q=Przemyslaw%20Dorozynski"> Przemyslaw Dorozynski</a>, <a href="https://publications.waset.org/abstracts/search?q=Barbara%20Gil"> Barbara Gil</a>, <a href="https://publications.waset.org/abstracts/search?q=Maciej%20Strzempek"> Maciej Strzempek</a>, <a href="https://publications.waset.org/abstracts/search?q=Bartosz%20Marszalek"> Bartosz Marszalek</a>, <a href="https://publications.waset.org/abstracts/search?q=Piotr%20Kulinowski"> Piotr Kulinowski</a>, <a href="https://publications.waset.org/abstracts/search?q=Wladyslaw%20Piotr%20Weglarz"> Wladyslaw Piotr Weglarz</a>, <a href="https://publications.waset.org/abstracts/search?q=Elzbieta%20Menaszek"> Elzbieta Menaszek</a> </p> <p class="card-text"><strong>Abstract:</strong></p> MOFs (Metal-Organic Frameworks) belong to a new group of porous materials with a hybrid organic-inorganic construction. Their structure is a network consisting of metal cations or clusters (acting as metallic centers, nodes) and the organic linkers between nodes. The interest in MOFs is primarily associated with the use of their well-developed surface and large porous. Possibility to build MOFs of biocompatible components let to use them as potential drug carriers. Furthermore, forming MOFs structure from cations possessing paramagnetic properties (e.g. iron cations) allows to use them as MRI (Magnetic Resonance Imaging) contrast agents. The concept of formation of particles that combine the ability to transfer active substance with imaging properties has been called theranostic (from words combination therapy and diagnostics). By building MOF structure from iron cations it is possible to use them as theranostic agents and monitoring the distribution of the active substance after administration in real time. In the study iron-MOF: Fe-MIL-101-NH2 was chosen, consisting of iron cluster in nodes of the structure and amino-terephthalic acid as a linker. The aim of the study was to investigate the possibility of applying Fe-MIL-101-NH2 as inhalable theranostic particulate system for the first-line anti-tuberculosis antibiotic – isoniazid. The drug content incorporated into Fe-MIL-101-NH2 was evaluated by dissolution study using spectrophotometric method. Results showed isoniazid encapsulation efficiency – ca. 12.5% wt. Possibility of Fe-MIL-101-NH2 application as the MRI contrast agent was demonstrated by magnetic resonance tomography. FeMIL-101-NH2 effectively shortening T1 and T2 relaxation times (increasing R1 and R2 relaxation rates) linearly with the concentrations of suspended material. Images obtained using multi-echo magnetic resonance imaging sequence revealed possibility to use FeMIL-101-NH2 as positive and negative contrasts depending on applied repetition time. MOFs micronization via ultrasound was evaluated by XRD, nitrogen adsorption, FTIR, SEM imaging and did not influence their crystal shape and size. Ultrasonication let to break the aggregates and achieve very homogeneously looking SEM images. MOFs cytotoxicity was evaluated in in vitro test with a highly sensitive resazurin based reagent PrestoBlue™ on L929 fibroblast cell line. After 24h no inhibition of cell proliferation was observed. All results proved potential possibility of application of ironMOFs as an isoniazid carrier and as MRI contrast agent in inhalatory treatment of tuberculosis. Acknowledgments: Authors gratefully acknowledge the National Science Center Poland for providing financial support, grant no 2014/15/B/ST5/04498. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=imaging%20agents" title="imaging agents">imaging agents</a>, <a href="https://publications.waset.org/abstracts/search?q=metal-organic%20frameworks" title=" metal-organic frameworks"> metal-organic frameworks</a>, <a href="https://publications.waset.org/abstracts/search?q=theranostics" title=" theranostics"> theranostics</a>, <a href="https://publications.waset.org/abstracts/search?q=tuberculosis" title=" tuberculosis"> tuberculosis</a> </p> <a href="https://publications.waset.org/abstracts/58754/iron-metal-organic-frameworks-potential-application-as-theranostics-for-inhalable-therapy-of-tuberculosis" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/58754.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">251</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">60</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">59</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">58</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">57</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">56</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">55</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">54</span> Influence of Heliotropium Undulatum on Hepatic Glutathione Conjugating Enzymes System in Acetylhydrazide-Rats</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=S.%20Ameddah">S. Ameddah</a>, <a href="https://publications.waset.org/abstracts/search?q=O.%20Deffa"> O. Deffa</a>, <a href="https://publications.waset.org/abstracts/search?q=H.%20Aissaoui"> H. Aissaoui</a>, <a href="https://publications.waset.org/abstracts/search?q=A.%20Menad"> A. Menad</a>, <a href="https://publications.waset.org/abstracts/search?q=R.%20Mekkiou"> R. Mekkiou</a>, <a href="https://publications.waset.org/abstracts/search?q=F.%20Benayache"> F. Benayache</a>, <a href="https://publications.waset.org/abstracts/search?q=S.%20Benayache"> S. Benayache </a> </p> <p class="card-text"><strong>Abstract:</strong></p> Acetylhydrazide (ACHD) is a metabolite of the anti-tubercular drug isoniazid (INH) that has been implicated in liver damage. This study was designed to evaluate hapatoprotective of n-BuOH extract of Heliotrpium undulatum (HUBE) in ACHD hepatotoxicity in rats. Hepatic damage was induced by administration of ACHD (300 mg/Kg op). The protection was affected by the administration of HUBE (200 mg/Kg op) for 14 days before ACHD administration, caused a decrease in LPO levels and in the transaminase and ALP levels and restored the GSH and its related enzymes (GPx, GST, GR) (50-62 %). Simultaneous administration of HUBE afforded a partial protection in statue of hepatic GSH conjugating enzymes upon administration of ACHD. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=heliotrpium%20undulatum" title="heliotrpium undulatum">heliotrpium undulatum</a>, <a href="https://publications.waset.org/abstracts/search?q=acetylhydrazide" title=" acetylhydrazide"> acetylhydrazide</a>, <a href="https://publications.waset.org/abstracts/search?q=glutathione%20conjugating%20enzymes" title=" glutathione conjugating enzymes"> glutathione conjugating enzymes</a>, <a href="https://publications.waset.org/abstracts/search?q=oxydatif%20stress" title=" oxydatif stress"> oxydatif stress</a>, <a href="https://publications.waset.org/abstracts/search?q=heaptoprotectif%20effect" title=" heaptoprotectif effect"> heaptoprotectif effect</a> </p> <a href="https://publications.waset.org/abstracts/40515/influence-of-heliotropium-undulatum-on-hepatic-glutathione-conjugating-enzymes-system-in-acetylhydrazide-rats" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/40515.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">312</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> 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> <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=isoniazid%20pharmacokinetics&page=2">2</a></li> <li class="page-item"><a class="page-link" href="https://publications.waset.org/abstracts/search?q=isoniazid%20pharmacokinetics&page=3">3</a></li> <li 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