[关键词]
[摘要]
目的 研究银杏内酯滴丸中的主要成分银杏内酯A、B在健康受试者体内的药动学特征,为制定合理的临床给药方案提供依据。方法 采用随机、开放的试验设计,10例健康受试者单次口服银杏内酯滴丸后,按预定时间点采集血样,肝素锂抗凝,离心分离血浆。采用LC-MS/MS法测定血浆样品中银杏内酯A、B的开闭环总质量浓度,以及银杏内酯A、B闭环质量浓度,并应用WinNonlin 6.3软件非房室模型计算药动学参数。结果 健康受试者单次口服银杏内酯滴丸后,银杏内酯A闭环及开闭环总量的tmax分别为(3.05±1.40)、(3.40±1.22)h,Cmax分别为(84.3±32.8)、(92.2±35.0)ng/mL,Cmax比值为91.4%,AUC0~t分别为(636±183)、(753±205)ng·h/mL,AUC0~t比值为84.5%,t1/2分别为(13.00±10.30)、(12.90±8.49)h;银杏内酯B闭环及开闭环总量的tmax分别为(3.15±1.42)、(3.35±1.25)h,Cmax分别为(74.10±31.50)、(148.00±60.10)ng/mL,Cmax比值为50.1%,AUC0~t分别为(627±202)、(1 410±431)ng·h/mL,AUC0~t比值为44.5%,t1/2分别为(13.20±5.83)、(13.7±5.83)h。结论 健康受试者口服银杏内酯滴丸后,银杏内酯A、B吸收速率适中,消除速率适中,在人血浆中银杏内酯A主要以闭环形式存在,而银杏内酯B以开、闭环2种形式存在、暴露量相当。
[Key word]
[Abstract]
Objective In order to describe the pharmacokinetic profiles of two effective constituents ginkgolide A and ginkgolide B in healthy subjects, and to provide supports for setting out the clinical application of Ginkgolides Dropping Pills. Methods Ten healthy subjects were enrolled in a randomized and open experimental design. Following a single oral administration of Ginkgolides Dropping Pills, blood samples which were anticoagulated by heparin sodium were collected at predetermined time, and then centrifuged to separate plasma samples. The total concentration of ginkgolide A and ginkgolide B in plasma samples and the lactone concentration of ginkgolide A and ginkgolide B were determined by a verified LC-MS/MS method, the pharmacokinetic parameters were calculated by WinNonlin 6.3 with non-compartment model. Results After a single oral administration of Ginkgolides Dropping Pills, the tmax of lactone, total concentration of ginkgolide A respectively were (3.05 ±1.40), (3.40 ±1.22) h, the Cmax were (84.3 ±32.8), (92.2 ±35.0) ng/mL, respectively, and its Cmax ratio was 91.4%. The AUC0-t were (636 ±183), (753 ±205) ng∙h/mL, respectively, and its AUC0-t ratio was 84.5%, half-life time (t1/2) were (13.0 ±10.3), (12.9 ±8.49) h, respectively. The Tmax of lactone, total concentration of ginkgolide B were (3.15 ±1.42), (3.35 ±1.25) h, The Cmax were (74.1 ±31.5), (148 ±60.1) ng/mL, respectively, and its Cmax ratio was 50.1%.The AUC0-t were (627 ±202), (1410 ±431) ng∙h/mL, respectively, and its AUC0-t ratio was 44.5%, t1/2 were (13.2 ±5.83), (13.7 ±5.83) h, respectively. Conclusion The results demonstrated that ginkgolide A and ginkgolide B were both at a moderate absorption and elimination rate, ginkgolide A mainly existed in human plasma upon lactone, while ginkgolide B presented as hydrolyzed forms with one or two lactone groups hydrolyzed and lactone, and the two forms of ginkgolide B were at equal exposure level after single oral administration of Ginkgolides Dropping Pills.
[中图分类号]
R285.61
[基金项目]
中国医学科学院药物代谢新技术创新单元(2019RU009)