Takeda S, Isono T, Wakui Y, Matsuzaki Y, Sasaki H, Amagaya S, Maruno M
Drug Safety and Metabolism Department, Tsumura Central Research Laboratories, Tsumura & Co., Ibaraki, Japan.
J Pharm Pharmacol. 1995 Dec;47(12A):1036-40. doi: 10.1111/j.2042-7158.1995.tb03293.x.
The absorption and excretion of paeoniflorin after intravenous and oral administration was studied in rats to evaluate the significance of paeoniflorin in the pharmacological action of Paeony root. The plasma concentration of paeoniflorin after intravenous administration at the doses of 0.5, 2.0 and 5.0 mg kg-1 rapidly decreased, simulated by a biexponential curve, with mean terminal half-lives of 11.0, 9.9 and 12.6 min, respectively. The Vdss values were 0.332, 0. 384 and 0.423 L kg-1 and the CLtot values were 26.1, 31.2 and 30.3 mL min-1 kg-1 at each dose. When given orally at the same doses, the absolute bioavailability values (F) determined by the AUC were 0.032, 0.033 and 0.038, respectively. The cumulative urinary and faecal excretions of paeoniflorin at the dose of 5 mg kg-1 after intravenous administration were 50.5 and 0.22% of the dose within 72 h, and 1.0 and 0.08% of the dose after oral administration within 48 h, respectively. Cumulative biliary excretion after intravenous or oral administration at a dose of 0.5 mg kg-1 was 6.9 and 1.3% of the dose within 24 h, respectively. The total CLR and CLB value after intravenous dosing was less than the CLtot value. These findings suggest that paeoniflorin is metabolized in other organs as well as in the liver. We conclude that paeoniflorin absorbed is excreted mainly in urine, it has a low bioavailability and the metabolites may be involved in the pharmacological action of Paeony root.
为评估芍药苷在芍药根药理作用中的重要性，研究了大鼠静脉注射和口服芍药苷后的吸收与排泄情况。静脉注射剂量为0.5、2.0和5.0 mg kg-1时，芍药苷的血浆浓度迅速下降，呈双指数曲线拟合，平均终末半衰期分别为11.0、9.9和12.6分钟。各剂量下的Vdss值分别为0.332、0.384和0.423 L kg-1，CLtot值分别为26.1、31.2和30.3 mL min-1 kg-1。以相同剂量口服时，通过AUC测定的绝对生物利用度值（F）分别为0.032、0.033和0.038。静脉注射5 mg kg-1剂量后，72小时内芍药苷的累积尿排泄量和粪便排泄量分别为给药剂量的50.5%和0.22%；口服给药后48小时内，分别为给药剂量的1.0%和0.08%。静脉注射或口服0.5 mg kg-1剂量后，24小时内累积胆汁排泄量分别为给药剂量的6.9%和1.3%。静脉给药后的总CLR和CLB值低于CLtot值。这些结果表明，芍药苷不仅在肝脏中代谢，在其他器官中也会代谢。我们得出结论，吸收后的芍药苷主要经尿液排泄，生物利用度低，其代谢产物可能参与芍药根的药理作用。
