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The pharmacokinetic behavior of glycyrrhizin after intravenous (i.v.), oral and intraperitoneal (i.p.) administration was compared in rats. The elimination half-life, total body clearance and volume of distribution at steady-state of glycyrrhizin were not significantly different among doses (2, 10 and 50 mg/kg i.v.). Glycyrrhizin was only detected in the plasma (maximum level: 1.3 micrograms/ml) after oral administration of 50 mg/kg. From comparison of the area under the plasma concentration-time curves after i.v. and oral administration of 50 mg/kg, the bioavailability of glycyrrhizin was estimated to be approximately 1%. Glycyrrhizin was stable for at least 3 h in gastric juice. The plasma concentration of glycyrrhizin after oral administration to neomycin-treated rats was not significantly different from that after administration to untreated rats. Furthermore, in in situ absorption study the cumulative ratio of glycyrrhizin in the mesenteric venous plasma after injection was only 1-2% of the dose. From these results, it appeared that the extremely low bioavailability by the oral route may be due to poor absorption of glycyrrhizin from the intestinal tract. On the other hand, the plasma concentration of glycyrrhizin rapidly increased after i.p. administration of doses of 2, 10 and 50 mg/kg, and reached a maximum level (4.7, 33.0 and 238.9 micrograms/ml, respectively) within 30 min. The bioavailability (65-90%) of glycyrrhizin after i.p. administration was enhanced dramatically. The i.p. route of administration may thus improve the bioavailability of glycyrrhizin.

Administration-Route Dependency of Absorption of Glycyrrhizin in Rats: Intraperitoneal Administration Dramatically Enhanced Bioavailability.