Disposition of glycyrrhizin in the perfused liver of rats.

The disposition of glycyrrhizin (GLZ) in the perfused liver of rats after dosing in the range of 0.5-30.0 mg was investigated and a pharmacokinetic model was devised to interpret the results. The uptake rate of GLZ into the liver with respect to the unbound GLZ concentration (Cf) in the perfusate followed a Michaelis-Menten type equation with a Km,up of 1.17 micrograms/ml and Vmax,up of 13.9 micrograms/min/g of liver. The efflux clearance (0.044 ml/min/g of liver) from the liver was independent of the Cf in the liver. The biliary excretion rate at a steady-state Cf level in the liver followed a Michaelis-Menten type equation with a substrate inhibition constant (Ki,B) of 42.3 micrograms/ml, Km,B of 1.68 micrograms/ml, and Vmax,B of 3.11 micrograms/min/g of liver. The proposed model, with the holding time fitted to biliary excretion at each dose, accurately described both the perfusate concentration-time profile and the cumulative biliary excretion profile.