丹参酚酸盐在健康志愿者的药代动力学和药效学研究

目的: 研究丹参酚酸盐在健康人体的药代动力学,以及血药浓度与血小板粘附性和聚集率的关系。方法: 9名健康志愿者根据交叉设计,静脉滴注丹参酚酸盐200、300、400 mg,用药后不同时间采血样,用高效液相色谱法测定丹参酚酸盐血药浓度;玻球法测定血小板粘附率;比浊法测定血小板聚集率。结果: 丹参酚酸盐药动学代谢呈二室模型,消除半衰期约lh,表观分布容积较大,提示为全身分布,峰浓度约为14 mg·L^-1。血小板粘附率在用药后呈波动性下降,5 h(即用药后4 h)药效渐渐消失,可见一个药效滞后环,在停药后3 h、血药浓度在1.91 mg·L^-1时药效达峰值。血小板粘附率在静滴药物期间与药浓相关,药效峰值与药浓岭值吻合,也呈现药效滞后环。结论: 丹参酚酸盐在健康人体消除快,对血小板聚集率和粘附率均有降低作用,前者达峰时间在滴注给药末,后者在停滴后3 h,均呈现较好的滞后效应。

Pharmacokinetics and pharmacodynamics research on salviol B in healthy volunteers

AIM: To study the pharmacokinetics and pharmacodynamics of salviol B in healthy volunteers and explore the relationship between the blood concentration of salviol B and the platelet aggregation and adhesiveness. METHODS: Nine male volunteers were administered 200, 300 and 400 mg salviol B (ivgtt) by cross-over design. The blood samples of different time points in these subjects were sampled and the drug concentrations of salviol B were analyzed by HPLC. The rates of platelet aggregation and adhesiveness were determined by efficacy indices. RESULTS: Salviol B was a two-compartment model with fast elimination (t_1/2, 1 h) and a large apparent volume of distribution. The C_maxwas 14 mg·L^-1. The rates of platelet aggregation and adhesiveness decreased after administration, and it was related to the change of drug concentration. The effect hysteresis rings were found from the curves of efficacy-concentration. CONCLUS-SION: Salviol B can decrease the rates of platelet ag-gregation and adhesiveness with efficacy hysteresis. It is an agent with fast elimination.