羟基红花黄色素A在健康人体中药效学与药动学研究

目的:研究羟基红花黄色素A(HSYA)在健康人体内的药效学及药动学(PD/PK)特征。方法:采用三交叉拉丁方设计,对9名健康志愿者按不同顺序分别静脉滴注注射用红花黄色素高、中、低剂量。用药后按不同时间点取静脉血检测血流变、凝血、血脂;超声彩色多普勒监测肝动脉、肾动脉及子宫动脉相应时间点的血流量;采用高效液相色谱-紫外检测法测定血浆药物浓度。结果:血液流变学、凝血用药前后有显著差异,脏器动脉血液灌注量用药前后有改善但不十分明显,初步判断该药起效时间为0.5~12h,中剂量最大药效时间3.5h。受试者血药浓度-时间数据用DAS2.0软件拟合,符合一级消除的二房室模型,主要药动学参数:Cm ax(实测值)按低、中、高剂量分别为(2.02±0.18)、(7.47±0.67)、(14.48±4.70)mg.L-1;t1/2β分别为(3.05±0.70)、(3.56±0.77)、(3.35±0.91)h;AUC0~15(以梯形法计算)分别为(6.79±1.29)、(26.75±5.46)、(49.81±13.75)μg.h.mL-1。结论:HSYA有改善血液流变学及抗凝血的作用,其体内代谢过程符合二室模型;高、中、低单剂量组的消除半衰期较快,体内平均驻留时间相近,AUC0~15、AUC0~∞和Cm ax均与剂量呈线性关系。

Pharmacodynamics and Pharmacokinetics of Hydroxy Safflor Yellow A in Healthy Volunteers

OBJECTIVE： To study the pharmacodynamics and pharmacokineties（PD/PK） of hydrosafflor yellow A （HSYA） in healthy volunteers. METHODS： By three- way crossover latin square design, 9 healthy volunteers were administered with high, medium and low dose of HSYA in different order by iv gtt. At different time point, the venous blood was sampled for detection of hemorheology, blood coagulation and blood lipid. The blood flow volume of hepatic artery, renal artery and uterine artery was measured by color doppler. The plasma drug concentration was determined by HPLC. RESULTS：As compared with before medication there were significant differences in hemorheology and blood coagulation after medication, and the blood flow volume of hepatic artery, renal artery and uterine artery improved but the difference was not significant. Our initial judgment of the time for HSYA to take effect was 0.5- 12 h; the maximum effective drug duration of medium dose was 3.5 h. The plasma drug concentration - time data calculated using DAS 2.0 software fitted two - compartment model with first order elimination. The main pharmacokinetic parameters for low, medium and high doses were as follows： Cmax （measured values） were（2.02± 0.18）, （7.47± 0.67） and（14.48± 4.70）μg · mL^-1, respectively; t1/2β were（3.05± 0.70） h, （3.56± 0.77） h and（ 3.35 ±0.91）h, respectively ; AUC0 -15（ computed by trapezoidal rule） were（ 6.79 ± 1.29）, （ 26.75 ± 5.46） and （ 49.81 ± 13.75）μg · h · mL^-1,respectively. CONCLUSION： HSYA can improve the hemorheology in addition to the antithrombotic action and its metabolic process in vivo fitted two - compartment model. HSYA at high, medium and lower dosages had rapid elimination half life and similar residence time in vivo. The AUC0-15,AUC0-∞ and Cmax assumed linear relationship with dosages of HSYA.