Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.

Masato Taguchi*, Misato Urai, Shigehiro Taira, Hiroko Tanabe, Yukiya Hashimoto

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism. The rate of metabolism in the liver microsomes in the presence of the plasma of BUL rats was also similar to that in the presence of the plasma of sham rats. These findings indicated that uremic substances which accumulate in BUL rats do not directly inhibit the activity of CYP2D2, which is responsible for the metabolism of metoprolol in the rat liver.

Original languageEnglish
Pages (from-to)156-164
Number of pages9
JournalDrug Metabolism and Pharmacokinetics
Volume21
Issue number2
DOIs
StatePublished - 2006/04

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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