The increased intestinal absorption rate is responsible for the reduced hepatic first-pass extraction of propranolol in rats with cisplatin-induced renal dysfunction

Hiromi Okabe, Akiko Mizukami, Masato Taguchi, Tetsuya Aiba, Masato Yasuhara, Yukiya Hashimoto

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The mechanisms responsible for the increased bioavailability of propranolol in renal dysfunction were investigated in rats. Experimental acute renal failure (ARF) was induced by intraperitoneal injection of cisplatin (5 mg kg-1). ARF induced a significant increase in blood propranolol concentration after intra-intestinal administration. The extent of bioavailability (F) of propranolol at an intestinal dose of 15 mg kg-1 was 16.4% and 26.9% in control and ARF rats, respectively, and the F value at a 37.5 mg kg-1 dose was 54.7% and 81.4% in control and ARF rats, respectively. In contrast, the blood propranolol concentration following intraportal infusion was not increased significantly in ARF rats. The hepatic first-pass extraction (Eh) was dose-dependent and saturable: Eh of propranolol in control rats was 58.0% and 18.3% at 8 and 20 mg kg-1, respectively, and Eh in ARF rats was 50.8% and 19.9% at 8 and 20 mg kg-1, respectively. The initial absorption rate of propranolol from the intestine in ARF rats was significantly greater compared with control rats. These results indicated that the increased bioavailability of propranolol in rats with cisplatin-induced renal dysfunction was mainly a result of the increased absorption rate in the intestine followed by the partial saturation of hepatic first-pass metabolism.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume55
Issue number4
DOIs
Publication statusPublished - Apr 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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