Disposition of Glycyrrhizin in the Perfused Liver of Rats

概要

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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 (C_f) in the perfusate followed a Michaelis-Menten type equation with a K_<m, up> of 1.17μg/ml and V_<max, up> of 13.9μg/min/g of liver. The efflux clearance (0.044ml/min/g of liver) from the liver was independent of the C_f in the liver. The biliary excretion rate at a steady-state C_f level in the liver followed a Michaelis-Menten type equation with a substrate inhibition constant (K_<i.B>) of 42.3μg/ml, K_<m, B> of 1.68μg/ml, and V_<max.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.
社団法人日本薬学会の論文
1994-07-15