Carrier-mediated hepatic uptake of a novel non-renal excretion type uric acid generation inhibitor, Y-700
スポンサーリンク
概要
- 論文の詳細を見る
発行後1年より著者最終稿を登録可能.Y-700, a novel xanthine oxidase inhibitor, was recently developed for the treatment of hyperuricemia and gout. Since the major elimination route of this compound is hepatic metabolism and excretion, the aim of the present study was to characterize the uptake mechanism of Y-700 in the liver, which is also the pharmacological target of Y-700. Efficient uptake of Y-700 was observed both in the liver in vivo and in isolated rat hepatocytes. The uptake was Na +-dependent, saturable and inhibited both by ATP-depressants and various organic anions. Indomethacin competitively inhibited Y-700 uptake, whereas the inhibitory effect of organic cations and nucleosides was not so remarkable. Saturable and Na+-dependent uptake of Y-700 was also observed in freshly isolated human hepatocytes. Uptake of Y-700 by sinusoidal membrane transporters, such as organic anion transporter (Oat) 2 and organic anion transporting polypeptide (OATP)-B, OATP-C, OATP-8, and Oatp1, could not be detected although uptake of Y-700 in the oocytes expressing sodium/taurocholate cotransporting polypeptide (NTCP) was slightly observed. In conclusion, active transport system(s), which specifically recognize certain types of anionic compounds, are involved in the hepatic uptake of Y-700 and, at least partially, relevant to its elimination from the circulation as well as delivery to pharmacological target. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association
論文 | ランダム
- Electrophysiologic Effects of Mexiletine in Children
- Reversal of Digoxin-Induced Changes in Erythrocyte Electrolyte Concentrations by Penicillamine in Children
- 461 稲麹に関する研究(第3報) : 稲麹菌の特性
- 麹菌の生産物が清酒酵母の香気生成の賦活に与える効果 : 酵母の生成する香気について(第11報)
- 組込みシステムのハードウェア技術(組込みシステム特集号)