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The pharmacokinetics of glycyrrhizin and its restorative effect on hepatic function in patients with chronic hepatitis and in chronically carbon‐tetrachloride‐intoxicated rats
Author(s) -
Yamamura Yoshikazu,
Kotaki Hajime,
Tanaka Naomi,
Aikawa Tatsuya,
Sawada Yasufumi,
Iga Tatsuji
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199711)18:8<717::aid-bdd54>3.0.co;2-u
Subject(s) - glycyrrhizin , carbon tetrachloride , chronic hepatic , pharmacokinetics , pharmacology , chronic hepatitis , liver function , ccl4 , medicine , chemistry , subcutaneous injection , hepatitis , endocrinology , cirrhosis , immunology , virus , organic chemistry
The relationships between the pharmacokinetic behaviour of glycyrrhizin and its restorative effect for hepatic function were investigated in patients with chronic hepatitis and in rats chronically treated with carbon tetrachloride (CCl 4 ‐treated rats). In patients, the restorative effects in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were 62·2±7·4 and 64·4±7·5%, respectively, after daily 80 mg intravenous (i.v.) doses of glycyrrhizin for 2 weeks, and 63·1±19·1 and 68·7±15·2% after 120 mg doses. The present work suggests that the threshold plasma glycyrrhizin concentration for sufficient effect is near 5 μg mL −1 . In rats, the total body clearance (Cl tot ) for glycyrrhizin in the CCl 4 ‐treated rats after i.v. administration of glycyrrhizin (5 mg kg −1 dose) was three‐tenths 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 between Cl tot and AST (r=−0·838) or ALT (r=−0·873) activity in both rats. When glycyrrhizin was administered intraperitoneally (i.p.) three times a week for 2 weeks, both the AST and ALT activities in the CCl 4 ‐treated rats showed a greater improvement than for a 10 mg kg −1 dose. Furthermore, the finding on the threshold plasma concentration in patients as above was also supported from the results of the experiments in rats. © 1997 John Wiley & Sons, Ltd.