1994 Volume 17 Issue 7 Pages 960-969
The dispostion of glycyrrhizin (GLZ) in the perfused liver of rats after dosing in the range of 0.5-30.0mg 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 1.17μg/ml and Vmax, up of 13.9μg/min/g of liver. The efflux clearance (0.044ml/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 42.3μg/ml, Km, B of 1.68μg/ml, and Vmax.B of 3.11μg/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.