Title: Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans
Abstract: Clinical Pharmacology & TherapeuticsVolume 58, Issue 6 p. 641-649 Pharmacokinetics and Drug Disposition Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans Man-Wai Lo PhD, Corresponding Author Man-Wai Lo PhD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USADepartment of Drug Metabolism, WP28-18, Merck Research Laboratories, West Point, PA, 19486.Search for more papers by this authorMichael R. Goldberg MD, PhD, Michael R. Goldberg MD, PhD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorJacqueline B. McCrea PharmD, Jacqueline B. McCrea PharmD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorHannah Lu BS, Hannah Lu BS Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorChristine I. Furtek BS, Christine I. Furtek BS Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorThorir D. Bjornsson MD, PhD, Thorir D. Bjornsson MD, PhD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this author Man-Wai Lo PhD, Corresponding Author Man-Wai Lo PhD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USADepartment of Drug Metabolism, WP28-18, Merck Research Laboratories, West Point, PA, 19486.Search for more papers by this authorMichael R. Goldberg MD, PhD, Michael R. Goldberg MD, PhD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorJacqueline B. McCrea PharmD, Jacqueline B. McCrea PharmD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorHannah Lu BS, Hannah Lu BS Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorChristine I. Furtek BS, Christine I. Furtek BS Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this authorThorir D. Bjornsson MD, PhD, Thorir D. Bjornsson MD, PhD Departments of Drug Metabolism and Clinical Pharmacology. Merck Research Laboratories, West Point Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USASearch for more papers by this author First published: December 1995 https://doi.org/10.1016/0009-9236(95)90020-9Citations: 34AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract The pharmacokinetics of the angiotensin II receptor antagonist losartan potassium and its active carboxylic acid metabolite EXP3174 were characterized in 18 healthy male subjects after administration of intravenous losartan, intravenous EXP3174, and oral losartan. In these subjects, the average plasma clearance of losartan was 610 ml/min, and the volume of distribution was 34 L. Renal clearance (70 ml/min) accounted for 12% of plasma clearance. Terminal half-life was 2.1 hours. In contrast, the average plasma clearance of EXP3174 was 47 ml/min, and its volume of distribution was 10 L. Renal clearance was 26 ml/min, which accounted for 55% of plasma clearance; terminal half-life was 6.3 hours. After oral administration of losartan, peak concentrations of losartan were reached in 1 hour. Peak concentrations of EXP3174 were reached in 312 hours. The area under the plasma concentration-time curve of EXP3174 was about four times that of losartan. The oral bioavailability of losartan tablets was 33%. The low bioavailability was mainly attributable to first-pass metabolism. After intravenous or oral administration of losartan the conversion of losartan to the metabolite EXP3174 was 14%. Clinical Pharmacology & Therapeutics (1995) 58, 641–649; doi: Citing Literature Volume58, Issue6December 1995Pages 641-649 RelatedInformation
Publication Year: 1995
Publication Date: 1995-12-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 263
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