Biliary excretion and enterohepatic cycling of glycyrrhizin in rats.

The enterohepatic cycling of glycyrrhizin was examined using rats with and without biliary fistulization. The plasma decay in the control rats without fistulization following an iv dose of 100 mg/kg of glycyrrhizin, was generally biphasic. However, secondary peaks were observed in all rats in the elimination phase, i.e., 0.5 to 12 h following dosing. The plasma concentrations in the rats with biliary fistulization administered the same dose showed a biexponential decline. The AUC and CLtot were significantly higher and lower in the control rats, respectively. The biliary excretion was 80.6 +/- 9.9% of the administered dose, and intestinal absorption was confirmed by using the bile collected after iv dosing. From these results, we concluded that glycyrrhizin was predominantly secreted from the liver into the bile, and that the secondary peaks in the elimination phase, the higher AUC, and the lower CLtot in the control rats were due to the effects of enterohepatic recycling of glycyrrhizin. Furthermore, the transport of the drug from the liver to the bile appears to be a saturable process.