BIOAVAILABILITY STUDY OF GLYCYRRHETIC ACID AFTER ORAL-ADMINISTRATION OF GLYCYRRHIZIN IN RATS - RELEVANCE TO THE INTESTINAL BACTERIAL HYDROLYSIS

To clarify the metabolic fate of glycyrrhizin when orally ingested, we investigated the bioavailability of glycyrrhetic acid, the aglycone o f glycyrrhizin, after intravenous or oral administration of glycyrrhet ic acid (5.7 mg kg(-1), equimolar to glycyrrhizin) or glycyrrhizin (10 mg kg(-1)) at a therapeutic dose in rat. Plasma concentration of glyc yrrhetic acid rapidly decreased after its intravenous administration, with AUC of 9200 +/- 1050 ng h mL(-1) and MRT of 1.1 +/- 0.2 h. The AU C and MRT values after oral administration were 10 600 +/- 1090 ng h m L(-1) and 9.3 +/- 0.6 h, respectively. After oral administration of gl ycyrrhizin, the parent compound was not detectable in plasma at any ti me, but glycyrrhetic acid was detected at a considerable concentration with AUC of 11 700 +/- 1580 ng h mL(-1) and MRT of 19.9 +/- 1.3 h, wh ile glycyrrhetic acid was not detected in plasma of germ-free rats at 12 h after oral administration of glycyrrhizin. The AUC value of glycy rrhetic acid after oral administration of glycyrrhizin was comparable with those after intravenous and oral administration of glycyrrhetic a cid, indicating a complete biotransformation of glycyrrhizin to glycyr rhetic acid by intestinal bacteria and a complete absorption of the re sulting glycyrrhetic acid from intestine. Plasma glycyrrhizin rapidly decreased and disappeared in 2 h after intravenous administration. AUC and MRT values were 2410 +/- 125 mu g min mL(-1) and 29.8 +/- 0.5 min , respectively. Plasma concentration of glycyrrhetic acid showed two p eaks, a small peak at 30 min and a large peak at 11.4 h, after intrave nous administration of glycyrrhizin, viith an AUC of 15 400 +/- 2620 n g h L(-1) and an MRT of 18.8 +/- 1.0 h. The plasma concentration profi le of the latter large peak was similar to that of glycyrrhetic acid a fter oral administration of glycyrrhizin, which slowly appeared and de clined. The difference of MRT values (19.9 and 9.3 h) for plasma glycy rrhetic acid after oral administration of glycyrrhizin and glycyrrheti c acid suggests the slow conversion of glycyrrhizin into glycyrrhetic acid in the intestine.