PHARMACOKINETIC PARAMETERS OF VERAPAMIL AND ITS ACTIVE METABOLITE NORVERAPAMIL IN PATIENTS WITH HEPATOPATHY

Verapamil (CAS 52-53-9) is a calcium channel blocker with a vasodilata tory effect. Because of its significant first-pass effect, verapamil m ight be advantageous in the treatment of portal hypertension. It does not produce any excessive systemic effects, provided the doses are sui tably adjusted. A decision was made to examine the pharmacokinetic par ameters independent of compartmental analysis of verapamil and its act ive metabolite norverapamil, inpatients with portal hypertension. Thei r Biological half-lives of the terminal phase were significantly prolo nged as compared with the control group. However, no statistically sig nificant differences were found in the values of t(max) and C-max. The calculated pharmacokinetic parameters of norverapamil were not signif icantly different from those of verapamil, except for the t(max) of no rverapamil, which, was significantly longer in patients suffering from portal hypertension as compared with verapamil. The ratio of areas un der the plasma concentration-time curve (AUG) of verapamil and norvera pamil was comparable in both groups of patients. No relationship betwe en the changes in the pharmacokinetic parameters and the extent of hep atic insufficiency was observed.