Moment analysis of drug disposition in kidney. II

Urine pH-dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney

A. Kamiya, Yusuke Tanigawara, Y. Saito, Y. Hayashi, T. Aiba, K. Inui, R. Hori

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Effects of urine pH on the renal tubular secretion of an organic cation (tetraethylammonium, TEA) and an organic anion (p-aminohippurate, PAH) were investigated using the isolated erythrocyte-perfused rat kidney. The method was based on a multiple indicator dilution experiment and noncompartmental moment analysis. Treatment with sodium bicarbonate and sodium dihydrogen phosphate increased and decreased urine pH, respectively, but affected neither the condition of the perfused kidney nor the renal handling of albumin and inulin. In TEA studies, the increase of urine pH prolonged the mean residence time in renal epithelial cells (T̄(cell)) and reduced the apparent secretion intrinsic clearance, but did not influence the volume of distribution in the kidney (Vd(drug)). The decrease of urine pH did not affect these kinetic parameters. By contrast, PAH secretion was constant against the change of urine pH. Since any change in the basolateral membrane transport is reflected in Vd(drug), the net transport from blood to cells can be regarded as similar under these treatments. On the other hand, the prolonged T̄(cell) of TEA with the increased urine pH suggested a slow transport from cells to lumen across the brush-border membranes. The present results coincide with the hypothelical mechanism that organic cations are secreted via an active transport system, coupled to the countertransport of H+ into cells. In conclusion, the present method is useful to separately evaluate the transmembrane transport across both sides of the renal epithelial cells in a morphologically intact kidney.

Original languageEnglish
Pages (from-to)692-697
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume79
Issue number8
DOIs
Publication statusPublished - 1990
Externally publishedYes

Fingerprint

Tetraethylammonium
p-Aminohippuric Acid
Rats
Urine
Kidney
Cations
Pharmaceutical Preparations
Membranes
Sodium Bicarbonate
T-cells
Inulin
Brushes
Kinetic parameters
Dilution
Anions
Albumins
Blood
Epithelial Cells
Active Biological Transport
Microvilli

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Moment analysis of drug disposition in kidney. II : Urine pH-dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney. / Kamiya, A.; Tanigawara, Yusuke; Saito, Y.; Hayashi, Y.; Aiba, T.; Inui, K.; Hori, R.

In: Journal of Pharmaceutical Sciences, Vol. 79, No. 8, 1990, p. 692-697.

Research output: Contribution to journalArticle

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