The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic function in patients with acute hepatitis and liver cirrhosis.
The pharmacokinetic behavior 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 (t1/2) 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 (CLtot) 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 t1/2 for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CLtot values were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CLtot and hepatic function (aspartate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CLtot for glycyrrhizin increased from 2.8 ml h-1 kg-1 to 11.4 mL h-1 kg-1, and the t1/2 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.
Yamamura
Y
Y
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Tanaka
N
N
Santa
T
T
Kotaki
H
H
Aikawa
T
T
Uchino
K
K
Osuga
T
T
Sawada
Y
Y
Iga
T
T
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019695:Glycyrrhizic Acid; D006207:Half-Life; D006505:Hepatitis / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019695:Glycyrrhizic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006034:Glycyrrhetinic Acid