达肝素钠注射液在中国健康人体的药效学研究  

Pharmacodynamics of sodiumhydroheparin injection in Chinese healthy volunteers

作　　者：林海琪 张希涛[1] 赵志霞[1] 李鹏飞[1] 于伟越[1] 杜萍[1] 刘洪川[1] 刘丽宏[1] 吕亚丽[1] LIN Hai-qi;ZHANG Xi-tao;ZHAO Zhi-xia;LI Peng-fei;YU Wei-yue;DU Ping;LIU Hong-chuan;LIU Li-hong;Lü Ya-li(Department of Pharmaceutical Affairs,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院药事部,北京100020

出　　处：《中国临床药理学杂志》2021年第21期2956-2960,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价受试与参比制剂达肝素钠注射液的药效学指标人体生物等效性,并评价参比制剂与受试制剂的安全性。方法本研究为开放、随机、两周期、双交叉、单次皮下注射和静脉注射给予达肝素钠注射液受试制剂或参比制剂的生物等效性试验。皮下注射给药(空腹)和静脉注射给药(空腹)的生物等效性试验。皮下注射给药和静脉注射给药正式试验各筛选24例健康成年受试者,按双交叉试验设计顺序进行给药,每个周期为单次给药。洗脱期7 d。利用各个时间点anti-Xa和anti-Ⅱa活性浓度评价受试制剂和参比制剂的药效学过程。结果静脉注射给药空腹状态下受试制剂和参比制剂基线校正后anti-Xa C_(max)分别为(0.79±0.08)和(0.78±0.09)U·mL^(-1);AUEC_(0-t)分别为(1.59±0.19)和(1.59±0.24)h·U·mL^(-1);AUEC_(0-∞)分别为(1.78±0.21)和(1.74±0.24)h·U·mL^(-1);皮下注射给药空腹状态下受试制剂和参比制剂基线校正后anti-Xa C_(max)分别为(0.68±0.08)和(0.68±0.10)U·mL^(-1);AUEC_(0-t)分别为(5.75±0.81)和(5.17±1.29)h·U·mL^(-1);AUEC_(0-∞)分别为(6.09±0.93)和(5.89±0.96)h·U·mL^(-1);研究表明受试制剂与参比制剂符合生物等效标准,研究期间发生的药物不良反应的严重程度均为轻度,受试制剂与参比制剂药物不良反应发生率接近。没有发生严重不良事件及严重药物不良反应。结论受试制剂与参比制剂符合生物等效标准,受试者对药物的耐受性良好,药物具有较好的安全性。Objective To evaluate the bioequivalence of sodiumhydroheparin injection test and reference produced and to evaluate the safety of reference preparation and test preparation.Methods This study was an open,randomized,two-cycle,double-crossover,single subcutaneous injection and intravenous injection of sodiumhydroheparin for bioequivalence test.The bioequivalence tests included subcutaneous injection(fasting)and intravenous injection(fasting).Twenty-four healthy adult volunteers were screened in the formal subcutaneous and intravenous administration tests.The drug was administered in the order of double cross-over design,and each cycle was given once.The cleaning period was 7 d between the two cycles.The pharmacodynamics of test and reference preparations were evaluated by the active concentrations of anti-Xa and anti-Ⅱa at each time point.Results After baseline correction of reagents and reference preparations on an intravenous fasting basis,anti-Xa C_(max) were respectively(0.79±0.08)and(0.78±0.09)U·mL^(-1);AUEC_(0-t) were(1.59±0.19)and(1.59±0.24)h·U·mL^(-1);AUEC_(0-∞)were(1.78±0.21)and(1.74±0.24)h·U·mL^(-1).After baseline correction of reagents and reference preparations in the state of subcutaneous injection on an empty stomach,anti-Xa Cm ax were(0.68±0.08)and(0.68±0.10)U·mL^(-1);AUEC0-t were(5.75±0.81)and(5.17±1.29)h·U·mL^(-1);AUEC_(0-∞)were(6.09±0.93)and(5.89±0.96)h·U·mL^(-1).The study showed that the test preparation and the reference preparation met the bioequivalence criteria.The severity of adverse reactions during the study period was mild,and the incidence of adverse reactions between the test preparation and the reference preparation was close.No serious adverse events and adverse reactions occurred.Conclusion The reference preparation and test preparation met the bioequivalent standard,the subjects were well tolerance with the drug,the drug was safe.

关 键 词：达肝素钠注射液 生物等效性 药代动力学 安全性 

分 类 号：R973[医药卫生—药品]