DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on May 13, 2009; DOI: 10.1124/dmd.109.026922

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.109.026922v1
37/8/1676    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Ogihara, T.
Right arrow Articles by Tamai, I.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ogihara, T.
Right arrow Articles by Tamai, I.


Received for publication January 29, 2009.
Revised May 10, 2009.
Accepted for publication May 11, 2009.

Oseltamivir (TamifluTM) is a substrate of PEPT1

Takuo Ogihara 1*, Takashi Kano 1, Tamae Wagatsuma 1, Sho Wada 1, Hikaru Yabuuchi 2, Shigeki Enomoto 2, Kaori Morimoto 1, Yoshiyuki Shirasaka 3, Shoko Kobayashi 1, Ikumi Tamai 3

1 Takasaki University of Health and Welfare 2 GenoMembrane, Inc. 3 Kanazawa University

* Address correspondence to: E-mail: togihara{at}takasaki-u.ac.jp

Abstract

Oseltamivir, an ester-type prodrug of the neuraminidase inhibitor Ro 64-0802, has been developed for the treatment of A and B strains of the influenza virus, but has neuropsychiatric and other side effects. In this study, we characterized the transport across intestinal epithelial cells and the absorption of oseltamivir in rats. Uptake by Caco-2 cells (human carcinoma cell line) and HeLa cells transfected with peptide transporter1 (HeLa/PEPT1) was time- and temperature-dependent, and was inhibited by typical PEPT1 inhibitors such as glycyl-sarcosine (Gly-Sar). The uptake by Caco-2 cells and HeLa/PEPT1 was saturable, with similar Km values. Oseltamivir absorption in adult rats was greatly reduced by simultaneous administration of milk, casein or Gly-Sar. Further, the plasma and brain concentrations of oseltamivir were higher in fasting than in non-fasting rats after oral administration. These results suggest that oseltamivir is a substrate of PEPT1, and that PEPT1 is involved in its intestinal absorption.


Key words: absorption, active transport, drug absorption, drug transport, intestinal bioavailability, intestinal transport, membrane transport, oral absorption, pharmacokinetics, prodrugs




Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2009 by the American Society for Pharmacology and Experimental Therapeutics.