氯吡格雷片比格犬体内的药物动力学  

Pharmacokinetics of clopidogrel tablets in beagle dogs

作　　者：胡维民[1] 张文颖[1] 程刚[1] 邹梅娟[1] 

机构地区：[1]沈阳药科大学药学院

出　　处：《中国药剂学杂志（网络版）》2009年第4期328-337,共10页Chinese Journal of Pharmaceutics：Online Edition

摘　　要：目的:采用液相色谱-串联质谱法,对受试制剂氯吡格雷片和参比制剂波立维进行比格犬体内药物动力学及生物利用度对照研究。方法:以氯雷他定为内标物质,采用双周期两制剂交叉实验设计,对6只比格犬给药,并对其体内血药浓度进行LC-MS/MS测定。结果:受试制剂和参比制剂中氯吡格雷的达峰时间tmax分别为(1.7±0.7))h(均值±标准差,下同)和(1.9±0.6)h,最大血药质量浓度ρmax分别为(1637.3±382.1)μg·L-1和(1663.0±472.2)μg·L-1,血药质量浓度-时间曲线下面积AUC0-t分别为(7622.8±2548.2)μg·h·L-1和(7876.6±2562.0)μg·h·L-1,AUC0-∞分别为(8128.5±2664.9)μg·h·L-1和(8563.4±2679.6)μg·h·L-1。以AUC0-t计算,与参比制剂相比,受试制剂的相对生物利用度为(99.3±25.5)%。结论:根据生物利用度和生物等效性试验的要求,受试制剂与参比制剂波立维比较,AUC0-t、ρmax、tmax符合生物等效性要求,但个体差异很大。Objective To study the pharmacokinetics and bioavailability of clopidogrel bisulfate tablets in beagle dogs using LC/MS/MS method,using PLAVIX(clopidogrel bisulfate tablets,Sanofi Winthrop Industrie) as the reference. Methods Using loratadine as the internal standard,double phase crossover experiment between two preparations was designed,and the plasma concentrations of six beagle dogs in vivo were determined. Results The time to peak (tmax) of clopidogrel in testing and reference preparations were (1.7 ± 0.7) h (Mean ± SD,the same below) and (1.9 ± 0.6) h,the maximum concentration (ρmax) in plasma were (1 637.3 ± 382.1) and (1 663.0 ± 472.2) μg·L-1,respectively. Calculated with trapezoidal rule,the area under concentration-time curve ( AUC0-t ) were ( 7 622.8 ± 2 548.2 ) and ( 7 876.6 ± 2 562.0 ) μg ·h·L-1; AUC0-∞ were ( 8 128.5 ± 2 664.9 ) and ( 8 563.4 ± 2 679.6) μg ·h·L-1,respectively. Based on AUC0-t,the bioavailability of the testing drug was (99.3 ± 25.5)% compared to the reference drug. Conclusion According to the regulations of bioavailability and bioequivalence,it was concluded that comparing to reference drug PLAVIX,the bioequivalence data (AUC0-t,ρmax and tmax) of the testing drug are acceptable,but have significant difference among individuals.

关 键 词：药剂学 药物动力学 生物利用度 高效液相-串联质谱 氯吡格雷 

分 类 号：R96[医药卫生—药理学]