The Pharmacokinetics of Nimodipine After Oral Administration in Rabbits with Hepatic Failure

Abstract

The pharmacokinetics of nimodipine, following a single 16 mg/kg oral dose, was investigated in rabbits with hepatic failure induced by 0.5 mL/kg (mild), 1.0 mL/kg (moderate) and 2.0 mL/kg (severe) of carbon tetrachloride : olive oil = 20 : 80, v/v). The plasma concentrations of nimodipine were determined by a high performance liquid chromatographic assay. The levels of sGOT and sGPT in rabbits with mild , moderate and severe hepatic failure were significantly increased compared to the control . The area under the plasma concentration-time curve (AUC) of nimodipine was significantly increased in mild , moderate and severe carbon tetrachloride-induced hepatic failure rabbits compared to the control (100%) rabbits. The volume of distribution and the total body clearance of nimodipine were significantly decreased in all hepatic failure groups. The elimination rate constant of nimodipine was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. There was a correlation between sGOT (y= 1.01x+241, r=0.993) or sGPT (y=0.92x +243, r=0.997) value and the AUC of nimodipine in the rabbits with hepatic failure. These findings suggest that the hepatic metabolism of nimodipine was inhibited by carbon tetrachloride-induced hepatic failure rabbits, resulting in the decrese in and of nimodipine in the rabbits with mild, moderate and severe hepatic failure.