Effects of probenecid and cimetidine on the renal excretion of 3'-azido- 3'-deoxythymidine in rats

Tetsuya Aiba, Y. Sakurai, S. Tsukada, T. Koizumi

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Abstract

The mechanisms underlying the inhibitory effects exerted by probenecid and cimetidine on the renal excretion of 3'-azido-3'-deoxythymidine (AZT) were investigated in rats in vivo. On i.v. administration, the findings indicated that both probenecid and cimetidine increased the plasma concentration of AZT and inhibited its renal excretion. To clarify the mechanisms underlying the interaction of these drugs with AZT and to elucidate the process of renal secretion of AZT, further investigation was performed, in which [3H]AZT (0.5 μM) was injected rapidly into the right renal artery, and its outflow profile from the right ureter was compared with that from the left ureter. In control experiments, 56.6% of the administered AZT was secreted from the right kidney, and it was calculated that the transcellular transit time of AZT in this process was 0.30 min. In the presence of 10 mM probenecid and of 10 mM cimetidine, the secretion of AZT was reduced to 15.3 and 32.3%, respectively, the inhibition induced by probenecid being more effective than that induced by cimetidine. However, the transcellular transit time of AZT increased to 0.53 and 1.21 min in the probenecid and cimetidine studies, respectively. Thus, cimetidine was more potent than probenecid in its effects on the transit time. These findings indicate that probenecid and cimetidine affect different steps in the renal secretion of AZT. It was therefore concluded that, on the renal plasma membrane, AZT is transported by anion transport systems, whereas on the brush border membrane, AZT is secreted by cation transport systems.

Original languageEnglish
Pages (from-to)94-99
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume272
Issue number1
Publication statusPublished - 1995
Externally publishedYes

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Probenecid
Zidovudine
Cimetidine
Kidney
Ureter
Secretory Pathway
Renal Artery
Microvilli
Renal Elimination
Drug Interactions
Anions
Cations
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Pharmacology

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Effects of probenecid and cimetidine on the renal excretion of 3'-azido- 3'-deoxythymidine in rats. / Aiba, Tetsuya; Sakurai, Y.; Tsukada, S.; Koizumi, T.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 272, No. 1, 1995, p. 94-99.

Research output: Contribution to journalArticle

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