Takeda S, Ishthara K, Wakui Y, Amagaya S, Maruno M, Akao T, Kobashi K
Drug Safety and Metabolism Department, Tsumura Central Research Laboratories, Tsumura & Co., Ibaraki, Japan.
J Pharm Pharmacol. 1996 Sep;48(9):902-5. doi: 10.1111/j.2042-7158.1996.tb05998.x.
To clarify the metabolic fate of glycyrrhizin when orally ingested, we investigated the bioavailability of glycyrrhetic acid, the aglycone of glycyrrhizin, after intravenous or oral administration of glycyrrhetic acid (5.7 mg kg-1, equimolar to glycyrrhizin) or glycyrrhizin (10 mg kg-1) at a therapeutic dose in rat. Plasma concentration of glycyrrhetic 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 AUC and MRT values after oral administration were 10600 +/- 1090 ng h mL-1 and 9.3 +/- 0.6 h, respectively. After oral administration of glycyrrhizin, the parent compound was not detectable in plasma at any time, but glycyrrhetic acid was detected at a considerable concentration with AUC of 11700 +/- 1580 ng h mL-1 and MRT of 19.9 +/- 1.3 h, while glycyrrhetic acid was not detected in plasma of germ-free rats at 12 h after oral administration of glycyrrhizin. The AUC value of glycyrrhetic acid after oral administration of glycyrrhizin was comparable with those after intravenous and oral administration of glycyrrhetic acid, indicating a complete biotransformation of glycyrrhizin to glycyrrhetic acid by intestinal bacteria and a complete absorption of the resulting glycyrrhetic acid from intestine. Plasma glycyrrhizin rapidly decreased and disappeared in 2 h after intravenous administration. AUC and MRT values were 2410 +/- 125 micrograms min mL-1 and 29.8 +/- 0.5 min, respectively. Plasma concentration of glycyrrhetic acid showed two peaks a small peak at 30 min and a large peak at 11.4 h, after intravenous administration of glycyrrhizin, with an AUC of 15400 +/- 2620 ng h L-1 and an MRT of 18.8 +/- 1.0 h. The plasma concentration profile of the latter large peak was similar to that of glycyrrhetic acid after oral administration of glycyrrhizin, which slowly appeared and declined. The difference of MRT values (19.9 and 9.3 h) for plasma glycyrrhetic acid after oral administration of glycyrrhizin and glycyrrhetic acid suggests the slow conversion of glycyrrhizin into glycyrrhetic acid in the intestine.
为阐明口服甘草酸苷后的代谢命运，我们在大鼠中以治疗剂量静脉注射或口服甘草次酸（5.7 mg kg-1，与甘草酸苷等摩尔）或甘草酸苷（10 mg kg-1）后，研究了甘草酸苷的苷元甘草次酸的生物利用度。静脉注射甘草次酸后，其血浆浓度迅速下降，AUC为9200±1050 ng h mL-1，MRT为1.1±0.2 h。口服后的AUC和MRT值分别为10600±1090 ng h mL-1和9.3±0.6 h。口服甘草酸苷后，血浆中在任何时间均未检测到母体化合物，但检测到了浓度可观的甘草次酸，AUC为11700±1580 ng h mL-1，MRT为19.9±1.3 h，而在口服甘草酸苷12小时后，无菌大鼠血浆中未检测到甘草次酸。口服甘草酸苷后甘草次酸的AUC值与静脉注射和口服甘草次酸后的AUC值相当，表明甘草酸苷在肠道细菌作用下完全生物转化为甘草次酸，且生成的甘草次酸从肠道完全吸收。静脉注射后，血浆中的甘草酸苷在2小时内迅速下降并消失。AUC和MRT值分别为2410±125微克 分钟 mL-1和29.8±0.5分钟。静脉注射甘草酸苷后，血浆中甘草次酸浓度出现两个峰值，30分钟时出现一个小峰值，11.4小时时出现一个大峰值，AUC为15400±2620 ng h L-1，MRT为18.8±1.0 h。后一个大峰值的血浆浓度曲线与口服甘草酸苷后甘草次酸的曲线相似，其出现和下降都较为缓慢。口服甘草酸苷和甘草次酸后血浆中甘草次酸的MRT值（19.9和9.3小时）的差异表明甘草酸苷在肠道中缓慢转化为甘草次酸。
