DISPOSITION OF GLYCYRRHIZIN IN THE PERFUSED LIVER OF RATS

The disposition of glycyrrhizin (GLZ) in the perfused liver of rats af ter dosing in the range of 0.5-30.0 mg was investigated and a pharmaco kinetic model was devised to interpret the results. The uptake rate of GLZ into the liver with respect to the unbound GLZ concentration (C(f )) in the perfusate followed a Michaelis-Menten type equation with a K (m,up) of 1.17 mug/ml and V(max) up of 13.9 mug/min/g of liver. The ef flux clearance (0.044 ml/min/g of liver) from the liver was independen t of the C(f) in the liver. The biliary excretion rate at a steady-sta te C(f) level in the liver followed a Michaelis-Menten type equation w ith a substrate inhibition constant (K(i,B)) of 42.3 mug/ml, K(m,B) of 1.68 mug/ml, and V(max,B) of 3.1/mug/min/g of liver. The proposed mod el, with the holding time fitted to biliary excretion at each dose, ac curately described both the perfusate concentration-time profile and t he cumulative biliary excretion profile.