Biotransformation of Ilaprazole in Human Liver Microsomes and Human: Role of CYP3A4 in Ilaprazole Clearance and Drug-Drug Interaction

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Jie PuMingshe Zhu

Abstract

Ilaprazole is a new proton pump inhibitor and is currently marketed in China and South Korea for the treatment of gastric and duodenal ulcer. Ilaprazole has a favorable long half-life and minimal pharmacokinetic variability associated with CYP2C19 polymorphism. Sulfoxide oxidation of ilaprazole is catalyzed mainly by CYP3A4. Thus, it has been widely accepted that CYP3A4 plays a major role in the clearance of ilaprazole in humans. However, absorption, distribution, metabolism, and excretion data of radiolabeled ilaprazole in humans are not available. The primary goal of this study was to determine if sulfoxide oxidation is a major metabolic pathway of ilaprazole in humans. Metabolite profiles of ilaprazole, ilaprazole sulfide, and ilaprazole sulfone in human liver microsomes (HLMs) were characterized and quantitively analyzed by liquid chromatography (LC)/UV/high-resolution mass spectrometry (HRMS). Moreover, metabolites of ilaprazole in human urine and feces were detected and identified by LC-HRMS. The results revealed that sulfoxide reduction to ilaprazole sulfide rather than sulfoxide oxidation was the major biotransformation pathway in HLMs. Sulfoxide reduction also occurred in HLMs without NADPH or in deactivated HLMs. Ilap...Continue Reading

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Citations

Jun 4, 2020·Anais Da Academia Brasileira De Ciências·Ibrahim Halil Gecibesler, Murat Aydin
Apr 10, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chongzhuang TangXiaoyan Chen
Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guiqiu ZhangChen Ma
Aug 27, 2021·Expert Opinion on Pharmacotherapy·Taraneh MousaviMohammad Abdollahi

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