Moment analysis of drug disposition in kidney. VI: Assessment of in vivo transmembrane transport of p-aminohippurate in tubular epithelium

Yan Ling He, Yusuke Tanigawara, Akira Kamiya, Ryohei Hori

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

This paper describes a novel method to assess the antiluminal membrane (ALM) and luminal membrane (LM) transport in vivo across renal tubular epithelial cells. The method is based upon a noncompartmental moment analysis of the plasma concentration and urinary excretion rate curves following renal artery injection. Quantitative relationships are represented between the noncompartmental parameters (clearance, volume of distribution, and the mean transit time) and the first-order rate constants associated with transmembrane transport processes. The in vivo transepithelial transport of [14C]p -aminohippurate (PAH) was examined using the rat kidney in the absence or presence of various plasma concentrations of unlabeled PAH, cefazolin, and methotrexate. The tubular secretion intrinsic clearance was reduced with an increase in the plasma concentration of concurrent unlabeled organic onions. The distribution volume of PAH in the kidney decreased in association with a decrease in the amount of PAH secreted, whereas the mean transepithelial (artery-to-lumen) transit time (-Tcell) remained constant. These findings indicate that ALM transport is a capacity-limited process determining the amount of tubular secretion, and that LM transport is linear over the concentration range examined and independent of the amount of secretion. The contribution of ALM and LM transport to transcellular transport was first clarified in vivo. The present method will be useful for analyzing the transmembrane transport processes in vivo for highly diffusible substances in the kidney.

Original languageEnglish
Pages (from-to)667-690
Number of pages24
JournalJournal of Pharmacokinetics and Biopharmaceutics
Volume19
Issue number6
DOIs
Publication statusPublished - 1991 Dec 1
Externally publishedYes

Keywords

  • antiluminal membrane transport
  • cefazolin
  • luminal membrane transport
  • methotrexate
  • organic anion
  • p-aminohippurate
  • transepithelial transport
  • tubular secretion

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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