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 vasodilatatory effect. Because of its significant first-pass effect, verapamil might be advantageous in the treatment of portal hypertension. It does not produce any excessive systemic effects, provided the doses are suitably adjusted. A decision was made to examine the pharmacokinetic parameters, independent of compartmental analysis of verapamil and its active metabolite norverapamil, in patients with portal hypertension. Their biological half-lives of the terminal phase were significantly prolonged as compared with the control group. However, no statistically significant differences were found in the values of tmax and Cmax. The calculated pharmacokinetic parameters of norverapamil were not significantly different from those of verapamil, except for the tmax of norverapamil, which was significantly longer in patients suffering from portal hypertension as compared with verapamil. The ratio of areas under the plasma concentration-time curve (AUC) of verapamil and norverapamil was comparable in both groups of patients. No relationship between the changes in the pharmacokinetic parameters and the extent of hepatic insufficiency was observed.
Vlcek
J
J
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
Macek
K
K
Hůlek
P
P
Brátová
M
M
Fendrich
Z
Z
D000328:Adult; D000368:Aged; D000983:Antipyrine / Q000493:pharmacokinetics; D001944:Breath Tests; D005260:Female; D006207:Half-Life; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014700:Verapamil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C016904:norverapamil; D014700:Verapamil; D000983:Antipyrine