中药复方塞络通中银杏内酯类成分的药代动力学及脑分布研究

Pharmacokinetics and Brain Distribution of Ginkgolides after Administration of Sai-Luo-Tong

目的：塞络通（SLT）是由人参、银杏叶、西红花组方,主治血管性痴呆的现代复方中药。为探讨SLT药效物质基础,并为给药方案提供依据,该文对治疗剂量SLT给与大鼠后,银杏内酯成分的血药浓度、药代特征、以及脑分布进行了研究。方法：实验建立了同时检测生物样品中4种银杏内酯的高灵敏度LCMS/MS分析方法,经过对线性、专属性、回收率、准确度、精密度的考察,所建立的分析方法符合临床前药代动力学研究要求。结果：灌胃SLT 60 mg·kg-1后,4种目标成分均在大鼠血浆中检出,各成分曲线下面积（AUC0-t）从大到小顺序依次为白果内酯（BB）、银杏内酯A（GA）、银杏内酯B（GB）和银杏内酯（GC）。银杏内酯的血浆消除半衰期（t1/2）较短,在1.61-2.82 h之间,其中BB半衰期最短。所有银杏内酯成分均能够快速进入在脑组织,GA和BB仍是脑组织中的主要成分。各银杏内酯在0.25、2、7 h的脑组织浓度均较同时间点血浆中药物成分低得多,且各成分在脑组织中浓度随时间下降较快。结论：研究结果表明,银杏内酯能够快速吸收进入体循环并进入脑组织,GA、BB和GB是其中主要的体内成分,它们能够共同作用于外周和脑组织,通过各自的药理活性机制达到塞络通对缺血性痴呆的疗效。

Sai-Luo-Tong （SLT） is a compound preparation composed of ginseng, ginkgo and saffron for the treatment of vascular dementia. In order to identify its material foundation and provide evidence for therapeutic regimen, the＂nbsp;plasma concentration, pharmacokinetics and brain distribution of ginkgolides were investigated after intragastric administration of SLT. An LC-MS/MS method was developed for the determination of 4 ginkgolides in rat plasma and brain simultaneously. Statistical analysis of obtained data demonstrated that the method had achieved the desired linearity, precision, accuracy and sensitivity. The results showed that after administration of SLT at the dose of 60 mg·kg-1, 4 ginkgolides were all absorbed into systemic circulation with AUC value in the order of bilobalide B （BB） 〉ginkgolide A （GA） 〉 ginkgolide B （GB） 〉 ginkgolide C （GC）. All ginkgolides exhibited short half lives less than 2.8 h among which BB showed the shortest t1/2 of 1.61 h. The determination of brain distribution at different time after dosing revealed ginkgolides entered into brain promptly dominated by GA and BB. The concentrations of 4 ginkgolides in brain were much lower than these in plasma and declined along with time rapidly. It was concluded that ginkgolides can be absorbed in blood and penetrated into brain rapidly. GA, BB and GB might be main components which effect both periphery and brain collectively by means of their specific mechanism to achieve the therapeutic efficacy on vascular dementia of SLT.