ADMINISTRATION ROUTE DEPENDENCY OF ABSORPTION OF GLYCYRRHIZIN IN RATS- INTRAPERITONEAL ADMINISTRATION DRAMATICALLY ENHANCED BIOAVAILABILITY

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 distribu tion 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 mu g/ml) after oral administration o f 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 bioav ailability of glycyrrhizin was estimated to be approximately 1%. Glycy rrhizin was stable for at least 3 h in gastric juice. The plasma conce ntration of glycyrrhizin after oral administration to neomycin-treated rats was not significantly different from that after administration t o untreated rats. Furthermore, in in situ absorption study the cumulat ive ratio of glycyrrhizin in the mesenteric venous plasma after inject ion was only 1-2% of the dose. From these results, it appeared that th e extremely low bioavailability by the oral route may be due to poor a bsorption 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 mu g/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 impr ove the bioavailability of glycyrrhizin.