硫酸氢氯吡格雷片在中国健康人体的生物等效性研究

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 75 mg,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C _max分别为(1351.1±654.9)、(1184.6±607.7) ng/mL,AUC_{0-24 h}分别为(2642.0±1093.8)、(2780.6±1283.1) ng·h ·mL^-1,AUC_0-∞分别为(2867.8±1238.9)、(3003.3±1291.2) ng·h·mL^-1,t_1/2分别为(3.81±2.54)、(4.62±2.88) h,t_max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C_max经对数转换后进行多因素方差分析及双单侧t检验,t_max经非参数检验,结果显示两种制剂生物等效。

Bioequivalence of clopidogrel hydrogen sulfate tablets in healthy Chinese volunteers

AIM: To evaluate the bioequivalence of clopidogrel hydrogen sulfate tablets(Areplex and Poland) in healthy Chinese volunteers after a single dosage oral administration.METHODS: A single oral doses of 75 mg clopidogrel hydrogen sulfate tablets(test and reference) were given to 32 healthy Chinese volunteers 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 reference preparation were calculated by analysis of variance, tow one sided t-test.RESULTS: The pharmacokinetic parameters of the two preparations were as follow:C_max of test drug and reference drug were(1351.1±654.9)ng/mL and (1184.6±607.7) ng/mL,AUC_0-24h were (2642.0±1093.8) ng·h·mL^-1 and (2780.6±1283.1) ng·h·mL^-1,t_1/2 were (3.81±2.54)h and (4.62±2.88) h,t_max 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,sensitive,rapid and convenient method that can be applied to determine clopidogrel in human plasma. The tested preparation is bioequivalence to the reference preparation.