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The Role of High Performance Liquid Chromatography in Identification of Rat Liver Microsomes Responsible for the in vitro Metabolite Formation of Dipyrone
<!DOCTYPE html> <html lang="en" dir="ltr"> <head> <!-- Google tag (gtag.js) --> <script async src="https://www.googletagmanager.com/gtag/js?id=G-P63WKM1TM1"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-P63WKM1TM1'); </script> <!-- Yandex.Metrika counter --> <script type="text/javascript" > (function(m,e,t,r,i,k,a){m[i]=m[i]||function(){(m[i].a=m[i].a||[]).push(arguments)}; m[i].l=1*new Date(); for (var j = 0; j < document.scripts.length; j++) {if (document.scripts[j].src === r) { return; }} k=e.createElement(t),a=e.getElementsByTagName(t)[0],k.async=1,k.src=r,a.parentNode.insertBefore(k,a)}) (window, document, "script", "https://mc.yandex.ru/metrika/tag.js", "ym"); ym(55165297, "init", { clickmap:false, trackLinks:true, accurateTrackBounce:true, webvisor:false }); </script> <noscript><div><img src="https://mc.yandex.ru/watch/55165297" style="position:absolute; left:-9999px;" alt="" /></div></noscript> <!-- /Yandex.Metrika counter --> <!-- Matomo --> <!-- End Matomo Code --> <title>The Role of High Performance Liquid Chromatography in Identification of Rat Liver Microsomes Responsible for the in vitro Metabolite Formation of Dipyrone</title> <meta name="description" content="The Role of High Performance Liquid Chromatography in Identification of Rat Liver Microsomes Responsible for the in vitro Metabolite Formation of Dipyrone"> <meta name="keywords" content="dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19"> <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" 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<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> 87356</div> </div> </div> </div> <div class="card publication-listing mt-3 mb-3"> <h5 class="card-header" style="font-size:.9rem">The Role of High Performance Liquid Chromatography in Identification of Rat Liver Microsomes Responsible for the in vitro Metabolite Formation of Dipyrone</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Salem%20Abdalla">Salem Abdalla</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 碌mol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis. <iframe src="https://publications.waset.org/abstracts/4983.pdf" style="width:100%; height:400px;" frameborder="0"></iframe> <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=dipyrone" title="dipyrone">dipyrone</a>, <a href="https://publications.waset.org/abstracts/search?q=4-methylaminoantipyrine%20%284-MAA%29" title=" 4-methylaminoantipyrine (4-MAA)"> 4-methylaminoantipyrine (4-MAA)</a>, <a href="https://publications.waset.org/abstracts/search?q=4-%20aminoantipyrine%20%284-AA%29" title=" 4- aminoantipyrine (4-AA)"> 4- aminoantipyrine (4-AA)</a>, <a href="https://publications.waset.org/abstracts/search?q=metabolism" title=" metabolism"> metabolism</a>, <a href="https://publications.waset.org/abstracts/search?q=human%20CYP2C19" title=" human CYP2C19"> human CYP2C19</a> </p> <a href="https://publications.waset.org/abstracts/4983/the-role-of-high-performance-liquid-chromatography-in-identification-of-rat-liver-microsomes-responsible-for-the-in-vitro-metabolite-formation-of-dipyrone" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/4983.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">238</span> </span> </div> </div> </div> </main> <footer> <div id="infolinks" class="pt-3 pb-2"> <div class="container"> <div style="background-color:#f5f5f5;" class="p-3"> <div class="row"> <div class="col-md-2"> <ul class="list-unstyled"> About <li><a href="https://waset.org/page/support">About Us</a></li> <li><a href="https://waset.org/page/support#legal-information">Legal</a></li> <li><a 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