THE RELATIONSHIP BETWEEN PHARMACOKINETIC BEHAVIOR OF GLYCYRRHIZIN AND HEPATIC-FUNCTION IN PATIENTS WITH ACUTE HEPATITIS AND LIVER-CIRRHOSIS

The pharmacokinetic behaviour of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycyrrhizin declined monoexponentially in both groups. The elimination half-life (t(1/2)) for glycyrrhizin in the hepatitis and cirrhosis groups varied significantly in the range of 2.7-7.6 h and 6.2-40.1 h, and the total body clearance (CL(tot)) in the range of 2.8-23.2 mL h(-1) kg(-1) and 1.4-12.9 mL h(-1) kg(-1), respectively. The t(1/2) for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CL(tot) values were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CL(tot) and hepatic function (aspartate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CL(tot) for glycyrrhizin increased from 2.8 ml h(-1) kg(-1) to 11.4 mL h(-1) kg(-1), and the t(1/2) shortened from 7.6 h to 3.4 h. These findings indicated that the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was closely related to the extent of the liver function.