目的 探讨银杏叶提取物对氯吡格雷人体内药动学影响及其相关机制。方法 选取14名健康男性志愿者,第一阶段服用氯吡格雷150 mg/d(单用药组);第二阶段进洗脱期后,受试者连续服用银杏叶提取物240 mg/d,连续14 d,第14天给予银杏叶提取物1 h后,再空腹服用氯吡格雷(联用药组)。两组均在给药后采集受试者0~24 h外周静脉血,检测氯吡格雷代谢产物SR-26334的浓度。此外,建立体外Caco-2细胞模型,以罗丹明-123和维拉帕米分别为阴性和阳性对照,采用流式细胞技术检测银杏叶提取物和氯吡格雷对Caco-2细胞内的荧光强度的影响。结果 联合用药组受试者血中SR26334的AUC(0-t)(3192.3±45.035)[(mg·h)/L]、AUC(0-∞)(3343.017±43.829)[(mg·h)/L]和Cmax(340.988±11.257)[(mg·h)/L]均高于单独用药组,CL/F(0.071±0.007)低于单独用药组(P<0.05)。Caco-2细胞内荧光强度,银杏叶提取物组(487±14.12)和联合用药组(497±17.22)高于阴性对照组(P<0.05)。结论 银杏叶提取物能显著提高氯吡格雷羧酸在人体内的生物利用度和吸收总量,其作用机制可能与银杏叶对P-糖蛋白(P-gp)的抑制作用有关。
Abstract
Objective To study the effects of Ginkgo biloba extract on pharmacokinetics of clopidogrel and its mechanism.Methods Fourteen healthy male volunteers took a single 100-mg oral dose of clopidogrel either alone or after pretreatment with 240 mg Ginkgo biloba extract daily for 14 days. On day 14, a single 100-mg oral dose of clopidogrel was administered. Plasma SR26334 concentrations of clopidogrel from zero to 24 h were measured by high-performance liquid chromatography.Results AUC(0-t)(3192.3±45.035), AUC(0-∞)(3343.017±43.829) and Cmax(340.988±11.257) of SR26334 in the combination group was significantly higher than that of the single-drug group (P<0.05).Conclusions Ginkgo biloba extractcan increase the bioavailability and absorption of clopidogrel. The mechanism may be related to Ginkgo biloba’s significant inhibition of P-glycoprotein.
关键词
银杏叶提取物 /
氯吡格雷 /
SR-26334 /
药动学
Key words
Ginkgo biloba /
clopidogrel /
SR-26334 /
pharmacokinetics
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