PT  - JOURNAL ARTICLE
AU  - Takuo Ogihara
AU  - Takashi Kano
AU  - Tamae Wagatsuma
AU  - Sho Wada
AU  - Hikaru Yabuuchi
AU  - Shigeki Enomoto
AU  - Kaori Morimoto
AU  - Yoshiyuki Shirasaka
AU  - Shoko Kobayashi
AU  - Ikumi Tamai
TI  - Oseltamivir (Tamiflu) Is a Substrate of Peptide Transporter 1
AID  - 10.1124/dmd.109.026922
DP  - 2009 Aug 01
TA  - Drug Metabolism and Disposition
PG  - 1676--1681
VI  - 37
IP  - 8
4099  - http://dmd.aspetjournals.org/content/37/8/1676.short
4100  - http://dmd.aspetjournals.org/content/37/8/1676.full
SO  - Drug Metab Dispos2009 Aug 01; 37
AB  - Oseltamivir, an ester-type prodrug of the neuraminidase inhibitor [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (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 transporter 1 (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. Furthermore, the plasma and brain concentrations of oseltamivir were higher in fasting than in nonfasting rats after oral administration. These results suggest that oseltamivir is a substrate of PEPT1 and that PEPT1 is involved in its intestinal absorption.