Verapamil effect on phenytoin pharmacokinetics in rats

These results suggested that VPM would have different impact on PHT pharmacokinetics, depending on the level of expression of both efflux transporters and enzymes. Before the hepatic cells could acquire a high content of enzymes due to the inductive effect of PHT dosing, VPM decreased the predominant intestinal clearance of PHT. But, once the enzymatic machinery at the hepatocyte became more important than that at the intestine, although ineffective because of the high hepatobiliary efflux transporter overexpression, VPM blockade from the liver resulted in an increased total PHT clearance.