Pharmacokinetics of Verapamil in Rabbits with Hepatic Disorder Induced by Carbon Tetrachloride

간장장애 가토에서 베라파밀의 약물동태

The purpose of this study was to investigate the pharmacokinetic changes of verapamil in rabbits with hepatic disorder induced by carbon tetrachloride. The plasma concentrations of verapamil were increased significantly (p<0.05, in slight group; P<0.01, in moderate and severe group) in all groups of hepatic disorder compared to the control group. Morover, the $C_{max}\;in\;slight\;(77.9\%$ increase), moderate ($110\%$ increase), and severe ($174\%$ increase) hepatic disorder groups were significantly (p<0.05, in slight; p<0.01, in moderate and severe) higher than that in control rabbits. These resulted in significantly (p<0.05, in slight; p<0.01, in moderate and severe) greater area under the plasma concentration-time curve (AUC) in moderate ($49.8\%$ increase), moderate ($95.0\%$ increase), and severe ($144\%$ increase) hepatic disorder groups than that in control rabbits. Hence, the relative bioavailability values were 149, 195, and $244\%$ for slight, moderate, and severe hepatic disorder groups, respectively. This could be due to decrease in metabolism of verapamil in the liver because of suppressed hepatic function in the hepatic disorder groups because verapamil is mainly metabolized in the liver.