Moment Analysis of Drug Disposition in Rat Kidney: Role of Basolateral Membrane Transport in Renal Transepithelial Transport of p‐Aminohippurate

Yoshihiro Saito, Yusuke Tanigawara, Noboru Okamura, Hiromasa Shimizu, Akira Kamiya, Ryohei Hori

研究成果: Article査読

8 被引用数 (Scopus)

抄録

Abstract— The determining step in transepithelial transport of p‐aminohippurate (PAH) in renal tubular secretion has been elucidated in the rat isolated perfused kidney. The method was based upon a multiple indicator dilution experiment and non‐compartmental moment analysis. Single‐pass dilution curves were obtained from venous and urinary effluents after simultaneous intra‐arterial injections of Evans blue with albumin, [3H]inulin and [14C]PAH. Probenecid was used as a transport inhibitor and dissolved in both perfusate and injection solution. The urinary excretion of PAH decreased depending on the probenecid concentration, while that of inulin was not affected. No correlation was observed between the amount of secretion and the mean residence time of secreted PAH in renal epithelial cells (T̈cell). Since T̈cell ought to be affected by the rate of secretion from cells to lumen, it was suggested that the secretion rate was independent of the amount secreted. In contrast, the amount of PAH excreted via tubular secretion showed a linear correlation with the volume of distribution in the kidney and the apparent rate constant for tubular uptake of PAH. Since these kinetic parameters reflect the transport from blood into cells across the basolateral membranes of renal epithelial cells, the present results demonstrated that basolateral membrane transport is a determining step in the transcellular transport of PAH and that the major effect of probenecid is the inhibition of transport from blood into cells. 1991 Royal Pharmaceutical Society of Great Britain

本文言語English
ページ(範囲)311-316
ページ数6
ジャーナルJournal of Pharmacy and Pharmacology
43
5
DOI
出版ステータスPublished - 1991 5月
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

フィンガープリント

「Moment Analysis of Drug Disposition in Rat Kidney: Role of Basolateral Membrane Transport in Renal Transepithelial Transport of p‐Aminohippurate」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル