Verapamil pharmacokinetics and liver function in patients with cirrhosis

In seven patients with liver cirrhosis, verapamil plasma levels were measured in blood drawn simultaneously from the hepatic vein and from an artery during the post-distributive phase after an intravenous bolus infusion of 5 mg of verapamil. In addition the hepatic plasma flow was measured using the indocyanine-green constant infusion technique. From these data the verapamil hepatic clearance and verapamil intrinsic clearance were calculated. The verapamil hepatic clearance was 423 +/- 92 ml/m, the hepatic plasma flow was 819 +/- 318 ml/m, and the verapamil intrinsic clearance was 1431 +/- 961 ml/m. As compared to values reported in the literature, a decrease of the verapamil hepatic clearance by 50% approximately was found, while the hepatic plasma flow was in the normal range and the verapamil intrinsic clearance was reduced by 75%. These data show that in patients with cirrhosis the decrease in verapamil clearance is due to an impairment in the capacity of the liver to remove the drug, and not to a decrease in liver perfusion.