Role of the intestinal peptide transporter PEPT1 in oseltamivir absorption: in vitro and in vivo studies.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Agnès PoirierFranz Schuler

Abstract

It was reported that oseltamivir (Tamiflu) absorption was mediated by human peptide transporter (hPEPT) 1. Understanding the exact mechanism(s) of absorption is important in the context of drug-drug and diet-drug interactions. Hence, we investigated the mechanism governing the intestinal absorption of oseltamivir and its active metabolite (oseltamivir carboxylate) in wild-type [Chinese hamster ovary (CHO)-K1] and hPEPT1-transfected cells (CHO-PEPT1), in pharmacokinetic studies in juvenile and adult rats, and in healthy volunteers. In vitro cell culture studies showed that the intracellular accumulation of oseltamivir and its carboxylate into CHO-PEPT1 and CHO-K1 was always similar under a variety of experimental conditions, demonstrating that these compounds are not substrates of hPEPT1. Furthermore, neither oseltamivir nor its active metabolite was capable of inhibiting Gly-Sar uptake in CHO-PEPT1 cells. In vivo pharmacokinetic studies in juvenile and adult rats showed that the disposition of oseltamivir and oseltamivir carboxylate, after oral administration of oseltamivir, was sensitive to the feed status but insensitive to the presence of milk and Gly-Sar. Moreover, oseltamivir and oseltamivir carboxylate exhibited significa...Continue Reading

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Citations

Apr 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yongjun HuDavid E Smith
Dec 1, 2015·Expert Review of Respiratory Medicine·Susanna Esposito, Nicola Principi
Feb 2, 2018·Journal of Animal Science and Biotechnology·Qingbiao XuJianxin Liu
Sep 1, 2018·European Journal of Clinical Pharmacology·Hannah Yejin KimAlan V Boddy
Apr 24, 2018·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·John P GleesonDavid J Brayden
Mar 21, 2017·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·John P GleesonSinéad M Ryan

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