Pharmacokinetics of glycyrrhizin and glycyrrhetic acid following glycyrrhizin administration to rats with single and multiple doses via different routes

Glycyrrhizin (GL) was administered to male rats, intravenously (i.v.), per os (p.o.) with a single bolus (10 mg/kg), or with multiple doses (2mg/kg each, every 24 hours), or intraperitoneally (i.p.) with a single bolus dose (10mg/kg). The plasma GL concentration-time curves obtained after single i.v. or i.p. GL injection closely resembled a 2-compartment model. The plasma GL and glycyrrhetic acid (GA) concentrations following single i.p. administration of GL changed almost identically to their changes following single i.v. case, despite some delay in peak time and a somewhat reduced peak concentration. In the single-dose p.o. case, the GL itself was absorbed very gradually and reached the maximum plasma concentration of about 70ng/mL 10-12h after administration. The amount absorbed up to 24 hours after administration was about 60% of the total. On the other hand, there was no significant difference in the GA behaviors after all routes of single GL administration. In the case of multiple GL doses, the plasma GL level was 2-10 μg/mL by the i.v. route, and 0.2-0.7 μg/mL for the p.o. administration. The plasma GA level was maintained at almost the same concentration ranging from 6-50ng/mL i.v. and 5-60ng/mL p.o., respectively. The results obtained in this study may be useful in establishing an optimal administration method for GL, when GL and GA would individually contribute to both the targeted effects and the adverse effects.