Pharmacokinetics of glycyrrhizin after intravenous administration to rats

A simple high-performance liquid chromatographic method was developed to study the pharmacokinetics of glycyrrhizin in the rat after bolus intravenous administration at a dose of 20, 50, or 100 mg/kg. The decline in the concentration of glycyrrhizin in plasma was generally biexponential at each dose, but the terminal disposition became much slower as the dose was increased. A greater-than-proportional increase in the glycyrrhizin concentration in plasma was observed with an increase in the dose, a result suggesting a dose-dependent glycyrrhizin disposition. The disposition of drug in plasma at each dose fitted well to a two-compartment pharmacokinetic model. The apparent total body clearance decreased significantly with increases in the dose. On the other hand, the apparent distribution volume after intravenous administration was unaffected by the dose. The results indicate that the pharmacokinetics of glycyrrhizin is nonlinear.