【作者】 曾志平；

【导师】 李焕德； 王实强；

【作者基本信息】 中南大学 ， 药剂学， 2009， 硕士

【摘要】 目的：按中药新药Ⅰ期临床药动学研究的指导原则,研究注射用羟基红花黄色素A的Ⅰ期药物动力学,为该药的Ⅱ期临床研究提供依据。方法：34名受试者男女各半随机分为3个单次(30 mg、45 mg、60 mg)给药组和一个(10人)多次给药组。用药后采用高效液相色谱紫外检测法分别测定4组受试者不同时间点血样的药物浓度以及单次给药中高剂量组尿样中药物的浓度。经DAS软件处理后,求出药动学参数。结果：60mg剂量组,0-3、3-6、6.12、12-24小时的排泄率分别为12.77±10.54%,13.2±4.11%,13.02±5.74%,5.2±3.32%,0-24小时的总排泄率为44.19±16.85%。对不同性别受试者的药物累积排泄率进行了F检验(P>0.05),男女排泄没有显著性差异。DAS软件分析,药物在体内随时间的变化符合一室模型,药动学参数用一室模型进行拟合计算。单次给药30mg、45mg、60mg剂量组羟基红花黄色素A的主要药动学参数分别为：Ke为0.338±0.092,0.215±0.036,0.229±0.0811/h;AUC(0-12)为5.285±0.574,10.666±4.325,14.259±3.314mg/L*h；AUC(0-∞)为6.712±0.837,13.501±5.732,17.109±3.87mg/L*h；t1/2为2.198±0.656,3.304±0.532,3.383±1.265h；V为14.253±4.285,19.315±10.051,18.115±7.64 L；CL为4.524±0.503,4.382±3.063,3.69±0.944 L/h。多次给药45mg的t1/2为2.7174,0.404h；AUCss为9.8634-4.416 mg／L*h；DF为5.363±0.821。对不同性别的受试者的t1/2、AUC(0-12)进行了F检验(P>0.05),性别对药物动力学参数没显著性差异。结论：羟基红花黄色素A药-时曲线符合一室模型,AUC和D之间呈正比关系,药动学参数t1/2、V、CL三个剂量组之间的差异经统计学处理无显著性差异(P>0.05),该药具有线性动力学特征。多次给药后体内无累加,部分以原形从肾脏排泄。更多还原

【Abstract】 OBJECTIVE:According to guidance of phase I clinical pharmacokinetics of new Chinese medcine, the phase I clinical pharmacokinetic study of hydroxysafflor yellow A was performed in order to prepare for the phaseⅡpharmacokinetics.METHODS:34 healthy volunteers consisting of 17 males and 17 females were randomly divided into four groups:Group One(10) was administrated hydroxysafflor yellow A for intravenously guttae time after time at dose level of 45mg; Group Two, Three and Four administrated only one time at dose levels of 30 mg、45 mg、60 mg respectively. High performance liquid chromatography (HPLC) with ultraviolet detection was applied to detect drug concentration in plasma of all groups and in urine of Group Four. Pharmacokinetics parameters were calculated with DAS software.RESULTS:The main pharmacokinetics parameters of test preparation were as follows:After a dose of 60mg, excretion rates of 0-3、3-6、6-12、2-24 hours in urine were 12.77±10.54%,13.2±4.11%, 13.02±5.74%,5.2±3.32% respectively, and the total excretion rate of 0-24 hour was 44.19±16.85%. F test was carried out to compare cumulative excretion rates of dose in male and female volunteers’urine, and the result had no statistic significance (P>0.05). All the serum concentration-time curves were fitted into one-compartment model. Parameters for Group Two to Four (30 mg,45 mg,60mg respectively) were as follows:Ke:0.338±0.092,0.215±0.036,0.229±0.0811/h; AUC(0-12):5.285±0.574,10.666±4.325,14.259±3.314 mg/L*h; AUC(0-∞):6.712±0.837,13.501±5.732,17.109±3.87 mg/L*h; t1/2: 2.198±0.656,3.304±0.532,3.383±1.265h; V:14.253±4.285,19.315±10.051,18.115±7.64 L; CL:4.524±0.503,4.382±3.063,3.69±0.944 L/h。In the multiple dose study, the main pharmacokinetics parameters of hydroxysafflor yellow A were as follows:t1/2:2.717±0.404h; AUCss: 9.863±4.416 mg/L*h; DF:5.363±0.821. F test was carried out to compare t1/2、AUC (0-12) of male and female volunteers, and the result had no statistic significance (P>0.05)CONCLUSION:The serum concentration—time curves of hydroxysafflor yellow A were fitted into one-compartment model. The AUC were in direct proportion with the dosage of drug. There was no significant difference in pharmacokinetic parameters between t1/2、V、CL of the three groups. Hydroxysafflor yellow A has linear dynamic feature. there was no accumulation after multiple dosing. It was partially excreted in the kidney.更多还原