国产硫酸氢氯吡格雷在中国健康受试者体内药代动力学和生物等效性研究

Pharmacokinetics and Bioequivalence Study of Domestic Made Clopidogrel in Healthy Chinese Volunteers

目的:研究硫酸氢氯吡格雷在中国健康受试者体内的药代动力学特性并评价其生物等效性。方法:23例中国男性健康受试者随机交叉单剂量口服泰嘉(国产硫酸氢氯比格雷,75mg/片,深圳信立泰药业股份有限公司生产)和波立维(原研厂硫酸氢氯比格雷,75mg/片,杭州赛诺菲—安万特制药有限公司)各150 mg后,采用高效液相色谱—串联质谱法测定血浆中氯吡格雷和氯吡格雷酸的浓度,并进行药代动力学和生物等效性研究。结果:口服泰嘉受试制剂者和波立维参比制剂者血浆中氯吡格雷血药达峰浓度(Cmax)分别为(3.07±3.63)ng/ml和(2.67±2.35)ng/ml;消除半衰期(t1/2)分别为(6.57±3.18)h和(6.96±3.92)h;药物浓度—时间曲线下面积(AUC)0-t分别为(4.75±4.68)ng.h/ml和(4.60±4.20)ng.h/ml。氯吡格雷酸的Cmax分别为(6 724±1 899)ng/ml和(6 262±1 968)ng/ml;t1/2分别为(8.77±1.20)h和(10.11±8.99)h;AUC0-t分别为(20 702±5 579)ng.h/ml和(19 817±4 232)ng.h/ml。口服泰嘉受试制剂者相比波立维参比制剂者氯吡格雷和氯吡格雷酸的相对生物利用度分别为(112.8±42.4)%和(107.4±31.6)%。结论:AUC0-t,AUC0-∞和Cmax经对数转换后,应用方差分析法、双单侧t检验及90%置信区间判断,两种制剂具有生物等效性。

Objective： To study the pharmacokinetics and bioequivalence of domestic made clopidogrel in healthy Chinese volunteers. Methods： The test formulation was Taijia, clopidogrel 75 mg tablet, and the reference formulation was Boliwei, clopidogrel 75 mg tablet. A single oral administration dose of 150 mg Taijia and 150 mg Boliwei were given to 23 healthy Chinese male volunteers by an open randomized crossover design. The plasma concentrations of clopidogrel and its main metabolite, clopidogrel acid were examined by liquid chromatography-tandem mass spectrometry to explore the pharmacokinetics and bioequivalence of two formulations. Results ： The main pharmacokinetic parameters of plasma clopidogrel in Test group and in Reference group ： the value of Cmax（3.07±3.63） and（2. 67±2. 35） ng/ml; t1/2（6. 57±3. 18） and（6.96±3.92） h;AUC0-t（4. 75±4. 68） and（4. 60±4. 20） ng · h/ml respectively. The main pharmacokinetic parameters of plasma clopidogrel acid in Test group and in Reference group：the value of Cmax（6 724±1 899） and（6 262± 1 968） ng/ml; t1/2 （ 8. 77 ±1. 20 ） and（ 10. 11 ±8. 99） h; AUC0-t （20 702±5 579） and（ 19 817± 4 232）ng · h/ml respectively. In test formulation to reference formulation, the relative bioavailability of clopidogrel and clopidogrel acid were （ 112. 8±42.4 ） % and （ 107.4±31.6 ） % respectively. Conclusion： Our work presented that two formulations have bioequivalenee by statistic analysis including two one-side t-test and 90% CI calculation.