Chronic verapamil administration alters phenytoin pharmacokinetics in the rat

Abstract

The interaction of verapamil (4 and 8 mg/kg twice daily for 7 days) and i.v. phenytoin (10 mg/kg) in male Wistar rats has been studied. Increases occurred in phenytoin plasma elimination half-life (61%; p < 0.01 and 80%; p < 0.05), the area under the plasma concentration curve (32% n.s. and 48; p < 0.05) and volume of distribution (17%; p < 0.05 and 14% n.s.) after 4 and 8 mg/kg verapamil, respectively. The clearance was reduced to 75% (n.s.) and 67% ( p < 0.05) of the control value; changes were not dose-dependent.