Pharmacokinetics of ipriflavone and its two metabolites, M1 and M5, after the intravenous and oral administration of ipriflavone to rat model of diabetes mellitus induced by streptozotocin

Abstract

Ipriflavone was reported to be primarily metabolized via hepatic cytochrome P450 (CYP) 1A1/2 and 2C11 in male Sprague-Dawley rats. The protein expression and/or mRNA levels of hepatic CYP1A subfamily and 2C11 was reported to be increased and decreased, respectively, in diabetic rats induced by streptozotocin (DMIS rats). Thus, the pharmacokinetic parameters of ipriflavone and its two metabolites, M1 and M5, were compared after the i.v. (20 mg/kg) and p.o. (200 mg/kg) administration of ipriflavone to control and DMIS rats. After both i.v. and p.o. administration of ipriflavone to DMIS rats, the AUCs of ipriflavone were significantly smaller (by 31.7% and 34.2% for i.v. and p.o. administration, respectively) than controls. The faster Cl-nr (smaller AUC) of i.v. ipriflavone could have been due to the faster hepatic Cl-int (because of an increase in the protein expression and/or mRNA level of hepatic CYP1A subfamily) and the faster hepatic blood flow rate than controls. The smaller AUC of p.o. ipriflavone in DMIS rats could have mainly been due to the faster intestinal Cl-int (because of an increase in the intestinal CYP1A subfamily) than controls. (C) 2009 Elsevier B.V. All rights reserved.