Pharmacokinetics of glycyrrhizin in rats with D-galactosamine-induced hepatic disease

The pharmacokinetic behavior of glycyrrihizin (GZ) was examined in D- galactosamine-intoxicated (GAL) rats. When GZ was administered intravenously, the apparent volume of distribution (Vd(ss)) and the total body clearance (CL(total)) were more significantly decreased in GAL rats than those in normal rats. When GZ was administered orally, the area under the plasma concentration-time curve (AUC), the mean residence time (MRT) and the time to reach the maximum plasma concentration (T(max)) for GZ were higher, but the maximum plasma concentration (Cp(max)) in GAL rats was lower than that in normal rats. The bioavailability of GZ, however, was not significantly changed. On the other hand, the AUC for glycyrrhetic acid (GA), a main metabolite of GZ, after oral administration of GZ was higher in GAL rats than in normal rats, although there was no significant difference in MRT or T(max), Cp(max) or the bioavailability for GA between GAL and normal rats. The reasons for these differences in GAL rats would be changes in the absorption rate (reduced gastric emptying rate) and reduction of the hepatic elimination rates (biliary excretion of GZ and hepatic metabolism of GA).