Pharmacokinetic changes of ipriflavone in rats with acute renal failure induced by uranyl nitrate

Abstract

Pharmacokinetic parameters of ipriflavone were compared after intravenous (20 mg/kg) and oral (200 mg/kg) administration in control rats and in rats with acute renal failure induced by uranyl nitrate (U-ARF rats). It was expected that the time-averaged nonrenal clearance (Cl-nr) of ipriflavone in U-ARF rats could be significantly slower than in the control rats, since it was reported that ipriflavone was metabolized via the hepatic microsomal cytochrome P450 (CYP) 1A1/2 and 2C11 and the expression and mRNA level of CYP1A2 were not changed, but those of CYP2C11 were decreased in U-ARF rats compared with control rats. Unexpectedly, after intravenous administration in U-ARF rats, the Cl-nr, of ipriflavone was significantly faster than in the controls (40.8 compared with 29.0ml/min/kg). This may be due to an increase in the glucuronide conjugate formation of ipriflavone metabolites in U-ARF rats. After oral administration of ipriflavone in U-ARF rats, the AUC(0-24h) was significantly smaller (194 compared with 295 mu g min/ml) than in the controls. Copyright (c) 2006 John Wiley & Sons, Ltd.