依诺肝素钠注射液在中国健康受试者的生物等效性研究

Bioequivalence of enoxaparin sodium injection in Chinese healthy volunteers

目的评估受试药物依诺肝素钠注射液和参比药物Clexane~?在中国健康受试者单次皮下注射给药后的相对生物利用度,评价受试药物和参比药物间的生物等效性。方法将24例健康受试者按照单剂量、开放、随机、双周期交叉设计,随机分为2组,单次皮下注射依诺肝素钠注射液受试药物与参比药物0. 4m L/4000 Axa U,用经验证的发色底物法测定人血浆中抗Ⅹa因子活性及血浆中抗Ⅱa因子活性,用Win Nonlin 6. 3软件按非房室模型计算药代动力学参数,并进行生物等效性评价。结果皮下注射受试和参比药物后,血浆抗Ⅹa的主要药代动力学参数如下:T_(1/2)分别为(3. 81±1. 19)和(3. 82±1. 37) h,T_(max)分别为(2. 94±0. 65)和(3. 15±0. 76) h,anti Ⅹ a_(max)分别为(0. 50±0. 09)和(0. 50±0. 08) U·m L^(-1);以AUEC_(0-∞)计算,受试药物的相对生物利用度为(99. 8±13. 6)%。血浆抗Ⅱa的主要药代动力学参数如下:T_(1/2)分别为(1. 96±0. 53)和(2. 03±0. 40) h,T_(max)分别为(3. 31±0. 61)和(3. 33±0. 48) h,antiⅡa_(max)分别为(0. 07±0. 02)和(0. 07±0. 02) U·m L^(-1),以AUEC_(0-∞)计算,受试药物的相对生物利用度为(103. 00±9. 15)%。结论单次空腹皮下给药试验结果表明受试药物与参比药物在健康受试者体内具有生物等效性。

Objective To evaluate the relative bioavailability of enoxaparin sodium injection and reference preparation Clexane?after single subcutaneous injection in Chinese healthy volunteers,and to evaluate the bioequivalence between the tested and reference preparations.Methods Twenty-four healthy subjects were randomly divided into two groups according to the single dose,open,random,double-cycle cross design.A single subcutaneous injection of enoxaparin sodium injection was given to the test preparation and reference preparation 0.4 m L/4000 Axa U.The activity of anti-Ⅹa and anti-Ⅱa in human plasma were determined by the method of certified chromogenic substrate,the pharmacokinetic parameters were calculated according to the non-atrioventricular model by WinNonlin 6.3 and the bioequivalence was evaluated.Results The main pharmacokinetic parameters of plasma anti-Ⅹa after subcutaneous injection were as follows:T1/2 were(3.81±1.19)and(3.82±1.37)h,Tmax were(2.94±0.65)and(3.15±0.76)h,Anti-Ⅹamax were(0.50±0.09)and(0.50±0.08)U·m L-1.The relative bioavailability of the tested preparation was(99.8±13.6)%calculated by AUEC0-∞.The main pharmacokinetic parameters of plasma anti-Ⅱa were as follows:T1/2 were(1.96±0.53)and(2.03±0.40)h,Tmax were(3.31±0.61)and(3.33±0.48)h,anti-Ⅱamax were(0.07±0.02)and(0.07±0.02)U·m L-1.The relative bioavailability of the tested preparation was(103.00±9.15)%calculated by AUEC0-∞.Conclusion The results of single fasting subcutaneous administration showed that the tested and reference preparations were bioequivalent in healthy volunteers.