银杏内酯滴丸在健康受试者体内的药动学研究

Clinical pharmacokinetics of Ginkgolides Dropping Pills in healthy subjects

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/m L,Cmax比值为50.1%,AUC0~t分别为(627±202)、(1410±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。

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/m L,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.