THE PHARMACOKINETICS OF GLYCYRRHIZIN AND ITS RESTORATIVE EFFECT ON HEPATIC-FUNCTION IN PATIENTS WITH CHRONIC HEPATITIS AND IN CHRONICALLY CARBON-TETRACHLORIDE-INTOXICATED RATS

The relationships between the pharmacokinetic behaviour of glycyrrhizi n and its restorative effect for hepatic function were investigated in patients with chronic hepatitis and in rats chronically treated with carbon tetrachloride (CCl4-treated rats). In patients, the restorative effects in plasma aspartate aminotransferase (AST) and alanine aminot ransferase (ALT) activities were 62.2 +/- 7.4 and 64.4 +/- 7.5%, respe ctively, after daily 80mg intravenous (i.v.) doses of glycyrrhizin for 2 weeks, and 63.1 +/- 19.1 and 68.7 +/- 15.2% after 120mg doses. The present work suggests that the threshold plasma glycyrrhizin concentra tion for sufficient effect is near 5 mu g mL(-1). In rats, the total b ody clearance (Cl-tot) for glycyrrhizin in the CCl4-treated rats after i.v. administration of glycyrrhizin (5mg kg(-1) dose) was three-tenth s of that of the control, and the t(1/2) for glycyrrhizin was 3.4-fold longer than that of the control. A good correlation was observed betw een Cl-tot and AST (r = -0.838) or ALT (r = -0.873) activity in both r ats. When glycyrrhizin was administered intraperitoneally (i.p.) three times a week for 2 weeks, both the AST and ALT activities in the CCl4 -treated rats showed a greater improvement than for a 10mg kg(-1) dose . Furthermore, the finding on the threshold plasma concentration in pa tients as above was also supported from the results of the experiments in rats. (C) 1997 John Wiley & Sons, Ltd.