Intestinal CYP3A4 is not involved in the enantioselective disposition of lansoprazole

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
M MiuraT Suzuki

Abstract

The contribution of (S)-lansoprazole to CYP3A4-catalysed sulfoxidation is greater than that of (R)-lansoprazole. The aim was to investigate the effect of grapefruit juice on the enantioselective disposition of lansoprazole among three CYP2C19 genotype groups. Eighteen healthy subjects, consisting of six each of homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs) and poor metabolizers (PMs), ingested a single oral dose of 60 mg racemic lansoprazole after taking either 200 ml grapefruit juice or water. There was no effect of grapefruit juice on the mean maximum plasma concentrations (C(max)) or the elimination half-life for each lansoprazole enantiomer in all three CYP2C19 genotype groups. Similarly, the pharmacokinetic parameters of lansoprazole sulfone remained unaltered by grapefruit juice in all three groups. The CYP3A4-mediated first-pass sulfoxidation of (R)- and (S)-lansoprazole were not influenced by grapefruit juice. In addition, stereoselectivity of the intestinal CYP3A4-catalysed sulfoxidation of (R)- and (S)-lansoprazole was not observed.

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Apr 15, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Masatomo MiuraToshio Suzuki
Jun 21, 2005·British Journal of Clinical Pharmacology·Masatomo MiuraToshio Suzuki

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Citations

Jun 7, 2006·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masatomo Miura
Dec 20, 2012·Expert Review of Molecular Diagnostics·Miao HuBrian Tomlinson
Jan 25, 2011·Expert Opinion on Drug Metabolism & Toxicology·Michael J HanleyDavid J Greenblatt
Mar 31, 2015·Evidence-based Complementary and Alternative Medicine : ECAM·Mou-Ze LiuWei Zhang
Jul 12, 2008·Molecular Nutrition & Food Research·Brian TomlinsonVivian W Y Lee
Apr 4, 2021·International Journal of Environmental Research and Public Health·Agnieszka WiesnerPaweł Paśko

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