Yamamura Y, Santa T, Kotaki H, Uchino K, Sawada Y, Iga T
University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Japan.
Biol Pharm Bull. 1995 Feb;18(2):337-41. doi: 10.1248/bpb.18.337.
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.
在大鼠中比较了甘草酸经静脉注射（i.v.）、口服和腹腔注射（i.p.）给药后的药代动力学行为。甘草酸的消除半衰期、全身清除率和稳态分布容积在剂量（2、10和50mg/kg静脉注射）之间无显著差异。口服50mg/kg后，仅在血浆中检测到甘草酸（最高水平：1.3微克/毫升）。通过比较静脉注射和口服50mg/kg后血浆浓度-时间曲线下的面积，估计甘草酸的生物利用度约为1%。甘草酸在胃液中至少稳定3小时。新霉素处理的大鼠口服给药后甘草酸的血浆浓度与未处理大鼠给药后的血浆浓度无显著差异。此外，在原位吸收研究中，注射后肠系膜静脉血浆中甘草酸的累积比例仅为剂量的1-2%。从这些结果来看，口服途径极低的生物利用度可能是由于甘草酸从肠道吸收不良所致。另一方面，腹腔注射2、10和50mg/kg剂量后，甘草酸的血浆浓度迅速升高，并在30分钟内达到最高水平（分别为4.7、33.0和238.9微克/毫升）。腹腔注射后甘草酸的生物利用度（65-90%）显著提高。因此，腹腔注射途径可能会提高甘草酸的生物利用度。
