摘要
目的:评价受试制剂硫酸氢氯吡格雷片(爱普瑞乐)与参比制剂硫酸氢氯吡格雷片(波立维)在中国健康人体中的生物等效性。方法:健康受试者双周期交叉空腹口服硫酸氢氯吡格雷片受试制剂和波立维片参比制剂75mg,用LC-MS/MS法测定氯吡格雷的羧酸代谢物氯吡格雷酸的血药浓度;用DAS 2.0软件进行数据处理,分析氯吡格雷酸人体药代动力学特征,来间接反应氯吡格雷的药代特征及生物等效性。结果:氯吡格雷的代谢物氯吡格雷酸的受试制剂与参比制剂的Cmax分别为(1351.1±654.9)、(1184.6±607.7)ng/mL,AUC0-24h分别为(2642.0±1093.8)、(2780.6±1283.1)ng·h·mL-1,AUC0-∞分别为(2867.8±1238.9)、(3003.3±1291.2)ng·h·mL-1,t1/2分别为(3.81±2.54)、(4.62±2.88)h,tmax分别为(0.80±0.32)、(0.95±0.63)h,受试制剂对参比制剂的相对生物利用度为(101.4±34.8)%。结论:本检测方法具有准确、灵敏、快速、简便等特点,适合人血浆中氯吡格雷酸浓度测定。AUC和Cmax经对数转换后进行多因素方差分析及双单侧t检验,tmax经非参数检验,结果显示两种制剂生物等效。
AIM： To evaluate the bioequiva- lence of clopidogrel hydrogen sulfate tablets （Areplex and Poland） in healthy Chinese volun- teers after a single dosage oral administration. METHODS： A single oral doses of 75 mg clopi- dogrel hydrogen sulfate tablets （test and refer- ence） were given to 32 healthy Chinese volun- teers according to an open randomized crossover design. The concentrations of clopidogrel acid （carboxylic metabolite of clopidogrel） in plasma were determined by LC-MS/MS. With the aid of DAS 2.0, the bioequivalence of the test and ref- erence preparation were calculated by analysis of variance, tow one sided t-test. RESULTS： The pharmacokinetic parameters of the two prepara- tions were as follow：Cmax of test drug and refer-ence drug were （1351.1±654.9） ng/mL and （ 1184.6 ± 607.7 ） ng/mL, AUC0-24h were （2642.0±1093.8） ng . h .mL-1 and （2780.6± 1283.1） ng .h . mL-1,t1/2 were （3.81±2.54）h and （4.62±2.88） h,tmax were （0.80±0.32） h and （0.95±0.63） h,respectively. The relative bioavailability of the formulation was （101.4±34.8）%. CONCLUSION. It is an accurate, sen- sitive, rapid and convenient method that can be applied to determine clopidogrel in human plas- ma. The tested preparation is bioequivalence to the reference preparation.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2014年第1期38-43,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
