银杏叶提取物对比格犬体内西洛他唑药动学的影响

Influence of extracts of the leaves of Ginkgo biloba on the pharmacokinetics of cilostazol in Beagle dogs

目的研究银杏叶提取物对西洛他唑体内药物动力学的影响。方法采用HPLC法测定单独给予西洛他唑后的比格犬体内药动学参数,并与同时给予西洛他唑和银杏叶提取物的药动学参数进行比较。根据生物利用度和生物等效性评价要求,分别对单独使用西洛他唑组、银杏叶提取物和西洛他唑合用组的AUC0～t与Cmax数据进行方差分析和双单侧t检验。结果药动学参数显示,单用组对于合用组,t1/2降低,Ke值升高,两个参数均有较为显著的改变;生物利用度和生物等效性的结果显示,AUC0～∞和AUC0～t不符合生物等效标准,Cmax符合生物等效性的要求。结论银杏叶提取物对西洛他唑的药动学参数有较大的影响,由于两种药物都有增加患者出血风险的可能性,因此在联合用药时应适当调整剂量,或者及时监测凝血时间以预测出血发生的可能性,防止不良反应的发生。

Objective To study effects of extracts of the leaves of Ginkgo biloba (GBE) on the pharmacokinetics of cilostazol. Methods The plasma concentrations of cilostazol were measured by using a validated HPLC method with a ultraviolet detector. Effects of GBE on the pharmacokinetic parameters of cilostazol in Beagle dogs were studied. Results According to the evaluation standards of bioequiavailability, 90% confidence interval (CI) for Cmax of cilostazol were in the predefined range of 0.7-1.43, the 90% CI for AUC0-t and AUC0-∞ were overlapped but ranged to the outside of the predefined range of 0.8-1.25. The results showed that Cmax of cilostazol were bioequivalent, while the AUC0-t and AUC0-∞ of cilostazol were not bioequivalent. Compared to the cilostazol combining GBE group, Ke increased and t1/2 decreased significantly in the cilostazol alone group. Conclusions The study showed that GBE has obvious effect on the pharmacokinetic parameters of cilostazol in vivo. It is suggested that the dose should be adjusted appropriately when GBE and cilostazol are used together in clinic to prevent potential adverse effects. Also, the clotting time should be monitored to reduce the risk of hemorrhage.