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  • Title: Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats.
    Author: Wu JW, Lin LC, Hung SC, Lin CH, Chi CW, Tsai TH.
    Journal: Drug Metab Dispos; 2008 Mar; 36(3):589-96. PubMed ID: 18048488.
    Abstract:
    Silibinin is the main biologically active flavonolignan extracted from the seeds and fruits of milk thistle and has potential efficacy in the treatment of liver disease. The aim of the present study was to examine the hepatobiliary excretion of silibinin and its effect on dimethylnitrosamine (DMN)-induced liver cirrhosis. The experiments were divided into five groups: 10, 30, and 50 mg/kg silibinin alone, 30 mg/kg silibinin coadministered with cyclosporin A (CsA), and 50 mg/kg silibinin with liver cirrhosis induced by DMN. The data indicated that silibinin had dose-related pharmacokinetics in the dose ranges of 10 to 50 mg/kg. All of the unconjugated or total (unconjugated + conjugated) silibinin concentrations in the bile were significantly higher than those in plasma at the sampling time points at each dose, suggesting active hepatobiliary excretion. When coadministered with CsA, the area under the concentration versus time curve (AUC) in bile was significantly decreased. This result suggested that the active silibinin efflux might be partially inhibited by P-glycoprotein. In the DMN-induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was reduced by 53%; however, total silibinin was increased by 182%. These results together suggest that the phase II conjugative reaction of silibinin was blocked by treatment with DNM.
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