Interactions of nonsteroidal anti-inflammatory drugs with rat renal organic anion transporter, OAT-K1

Satohiro Masuda, Hideyuki Saito, Ken Ichi Inui

研究成果: Contribution to journalArticle査読

51 被引用数 (Scopus)

抄録

We recently cloned and characterized the rat kidney-specific organic anion transporter, OAT-K1 which was suggested to mediate renal tubular transport of methotrexate. In this study, we investigated the interactions of nonsteroidal anti-inflammatory drugs (NSAIDs) with OAT-K1 by evaluating the effects of these drugs on renal distribution of methotrexate in vivo, and on methotrexate accumulation in the stably transfected LLC-PK1 cells expressing OAT-K1 (LLC-OAT-K1). NSAIDs such as indomethacin and ketoprofen had significant inhibitory effects on renal accumulation of methotrexate in rats after coadministration. Indomethacin and ketoprofen inhibited methotrexate accumulation by LLC-OAT-K1 cells in a competitive manner with the apparent inhibition constant values of 1.0 mM and 1.9 mM, respectively. Other NSAIDs including ibuprofen, flufenamate and phenylbutazone also showed potent inhibitory effects on methotrexate accumulation. However, indomethacin was not transported via OAT-K1. These results indicate that NSAIDs have potent inhibitory effects against the OAT-K1-mediated methotrexate transport, which suggests that the OAT-K1 may be one of interaction sites for methotrexate and NSAIDs in the kidney.

本文言語英語
ページ(範囲)1039-1042
ページ数4
ジャーナルJournal of Pharmacology and Experimental Therapeutics
283
3
出版ステータス出版済み - 12 1997
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学

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