IngentaConnect Effects of cytochrome P450 (CYP) inducers and inhibitors on ondan...

Authors: Yang, Si H.¹; Lee, Myung G.¹

Source: Journal of Pharmacy and Pharmacology, Volume 60, Number 7, July 2008 , pp. 853-861(9)

Abstract:

The types of hepatic microsomal cytochrome P450 (CYP) isozymes responsible for the in-vivo metabolism of ondansetron in rats have not been reported. In this study, ondansetron at a dose of 8 mg kg⁻¹ was administered intravenously to rats pretreated with various inducers of CYP isozymes, such as 3-methylcholanthrene, orphenadrine citrate, isoniazid and dexamethasone phosphate (the main inducers of CYP1A1/2, 2B1/2, 2E1 and 3A1/2 in rats, respectively), and inhibitors, such as SKF-525A (a non-specific inhibitor of CYP isozymes), sulfaphenazole, quinine hydrochloride and troleandomycin (the main inhibitors of CYP2C6, 2D subfamily and 3A1/2 in rats, respectively). In rats pretreated with quinine hydrochloride and troleandomycin, the time-averaged non-renal clearance of ondansetron was significantly slower (48.9 and 13.2% decrease, respectively) than that in control rats. In rats pretreated with dexamethasone phosphate, the time-averaged non-renal clearance was significantly faster (18.2% increase) than that in control rats. The results suggest that ondansetron is primarily metabolized via the CYP2D subfamily and 3A1/2 in rats.

Document Type: Research article

DOI: 10.1211/jpp.60.7.0006

Affiliations: 1: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Gwanak-Gu, Seoul 151-742, South Korea

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Effects of cytochrome P450 (CYP) inducers and inhibitors on ondansetron pharmacokinetics in rats: involvement of hepatic CYP2D subfamily and 3A1/2 in ondansetron metabolism