Pharmacokinetics of bicyclol in rats with acute hepatic failure

Abstract

The aim of present study is to evaluate the pharmacokinetics of bicyclol in carbon tetrachloride (CCl(4))-intoxicated rats. The plasma concentration of bicyclol was detected in rats after a single oral or intravenous administration by high-performance liquid chromatography (HPLC) analysis. Rat intestinal and hepatic perfusion models were employed to clarify the respective effect of gut and liver on the pharmacokinetics of bicyclol in acute hepatic failure (AHF) rats. Rat in vitro microsomal incubation was also conducted. The bioavailability of bicyclol was increased 3.1-fold after CCl(4) intoxication in rats. The area under the curve (AUC)((0-infinity)), C(max), and clearance (CL) of bicyclol after intravenous administration were 13.4 mg h l(-1), 18.8 mg l(-1), and 1.8 l h(-1) kg(-1) in control rats, and 130 mg h l(-1), 33.1 mg l(-1), and 0.15 l h(-1) kg(-1) in AHF rats, respectively. In the present study we investigated the pharmacokinetics of bicyclol in CCl(4)-intoxicated rats and differentiated the respective role of intestine and liver by using in situ intestinal and hepatic perfusion in rats, and in vitro rat microsomes incubation. The studies are expected to provide a better understanding related to the alteration of pharmacokinetics of bicyclol in pathological situation.