Oseltamivir (Tamiflu) is a substrate of peptide transporter 1

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

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1676-1681
Number of pages6
JournalDrug Metabolism and Disposition
Issue number8
Publication statusPublished - 08-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science


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