Methotrexate-Loxoprofen Interaction: Involvement of Human Organic Anion Transporters hOAT1 and hOAT3

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  • UWAI Yuichi
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • TANIGUCHI Risa
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • MOTOHASHI Hideyuki
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • SAITO Hideyuki
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • OKUDA Masahiro
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
  • INUI Ken-ichi
    Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

書誌事項

公開日
2004
資源種別
journal article
DOI
  • 10.2133/dmpk.19.369
公開者
日本薬物動態学会

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説明

Human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8) are responsible for renal tubular secretion of an antifolic acid methotrexate, and are considered to be involved in drug interaction of methotrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). In our hospital, a delay of methotrexate elimination was experienced in a patient with Hodgkin's disease, who took loxoprofen, a commonly used NSAID in Japan, which suggested a cause. In this study, we examined the drug interaction via hOAT1 and hOAT3, using Xenopus laevis oocytes. hOAT1 and hOAT3 mediated the methotrexate transport with low affinity (Km of 724.0 μM) and high affinity (Km of 17.2 μM), respectively. Loxoprofen and its trans-OH metabolite, an active major metabolite, markedly inhibited the methotrexate transport by both transporters. Their inhibition concentrations (IC50) were in the range of the therapeutic levels. These findings suggest that loxoprofen retards the elimination of methotrexate, at least in part, by inhibiting hOAT1 and hOAT3.<br>

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