Effects of water deprivation for 72 h on the pharmacokinetics of ipriflavone in rats

It has been reported that ipriflavone was primarily metabolized via hepatic microsomal cytochrome P450 (CYP) 1A1/2 and 2C11 in rats, and the expression of hepatic CYP1A2 and 2C11 was not changed in rats with water deprivation for 72 h compared to controls. Hence, it could be expected that the time-averaged nonrenal clearance (Clnr) of ipriflavone would be comparable between two groups of rat. As expected, after intravenous administration of ipriflavone (20 mg/kg), the Clnr values of ipriflavone were comparable between two groups of rat. This could be supported by comparable in vitro intrinsic clearance (Clint) values for the disappearance of ipriflavone in hepatic microsomes for both groups of rat. After oral administration of ipriflavone (200 mg/kg), the total area under the plasma concentration–time curve from time zero to the last measured time, 12 h, in plasma (AUC0–12 h) values of ipriflavone were also comparable between two groups of rat. The above data suggest that dehydration state did not affect significantly pharmacokinetics of ipriflavone in rats.