Hepatobiliary excretion of silibinin and liver damage induced by dimethylnitrosamine and the effect of silibinin on the pharmacokinetics of pyrazinamide

• Main Authors: Jhy-Wen Wu, 吳智文
• Other Authors: Tung-Hu Tsai
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/30093104246476693453

博士 === 國立陽明大學 === 傳統醫藥學研究所 === 95 === Silibinin is the main flavonoid extracted from milk thistle (Silybum marianum), and it displays hepatoprotective properties. Pyrazinamide (PZA) is widely used in combination with other drugs in chemotherapy for tuberculosis. However, the dose-related liver injury is the main adverse effect of PZA and its metabolite (pyrazinoic acid; PA). The aim of this study was to develop simple liquid chromatographic systems to assay silibinin, PZA and PA in plasma and bile for pharmacokinetic study, respectively and to investigates the pharmacokinetics and hepatobiliary excretion of silibinin and the effect of liver cirrhosis induced by dimethylnitrosamine and the effect of silibinin on the pharmacokinetics of pyrazinamide and pyrazinoic acid in rats. After silibinin had a given in rats, the disposition of silibinin in the plasma and bile fluid was rapid distribution and equilibration between the blood and hepatobiliary system, and the bile levels of unconjugated silibinin and total silibinin was greater than those in the plasma. The active silibinin efflux might be affected by P-gp because co-administration of Cyclosporin A significantly decreased the total silibinin AUC in the bile. After intravenous administration of silibinin to cirrhotic rats, the AUC of plasma total silibinin was significantly greater than the silibinin 50 mg kg-1 alone, due to decrease bile-to-blood distribution. The hepatobiliary elimination of PA may be affected by silibinin in the groups of long-term silibinin exposure and concomitant short-term silibinin exposure.