Moment analysis of drug disposition in kidney: Transcellular transport kinetics of p‐Aminohippurate in the Isolated Perfused Rat Kidney

Ryohei Hori, Yusuke Tanigawara, Yoshihiro Saito, Yoshie Hayashi, Tetsuya Aiba, Katsuhiko Okumura, Akira Kamiya

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Abstract

The mean renal epithelial cell residence time, T̄cell, was defined as a model‐independent characteristic of the transcellular transport process in the isolated perfused kidney. The transcellular transport process includes transport at the basolateral membrane, diffusion in the cytosol, and transport at the brush border membrane. The parameter T̄cell represents the mean time for the drug secreted from the tubules to pass through the renal epithelial cells, and is calculated as the difference of the mean urinary transit time between secreted drug and inulin in the single‐pass perfusion system. Therefore, the urinary excretion rate–time course is indispensable to evaluate T̄cell. p‐Amino‐hippuric acid was used as a model compound. The bovine erythrocytes in the perfusate kept the isolated kidney in an almost constant physiological condition, including secretion function. The renal vein outflow curves were also analyzed by the use of moments. The dispersion in the catheter was corrected by a deconvolution. The apparent secretion intrinsic clearance and the apparent volume of distribution were calculated from the moments. The present method will be useful for analysis of the transcellular transport mechanism and the effect of disease states on renal transport of drugs.

Original languageEnglish
Pages (from-to)471-476
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume77
Issue number6
DOIs
Publication statusPublished - 1988 Jun
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmaceutical Science

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