国产达肝素钠注射液在健康受试者的生物等效性及安全性

发布时间：2018-03-12 15:25

本文选题：达肝素钠注射液　切入点：生物等效性　出处：《中国新药杂志》2017年08期 　论文类型：期刊论文

【摘要】：目的:评价健康成年男性受试者单次腹壁皮下注射达肝素钠后的生物等效性和安全性。方法:本研究共选择健康受试者26例,2例参与预试验,24例纳入正式试验。试验采用随机、开放、单剂量、双周期交叉设计对国产达肝素钠注射液进行评价,受试者随机分为2组,第1周期分别皮下注射受试制剂或参比制剂,第2周期交叉给药,2个周期间隔时间7 d。受试者禁食过夜至少10 h后分别于腹壁皮下注射受试制剂或参比制剂0.2 m L∶5 000 IU,并于预定时间点采集血样。non-compartmental analysis法计算主要药动学参数:达肝素钠抗Xa和IIa因子E_(max),AUEC_(0~t),AUEC_(0~E),计算受试/参比制剂的90%置信区间。试验过程中行生命体征、实验室及心电图检查,并记录不良事件情况。26例受试者全部纳入安全分析集,24例正式试验者纳入符合方案集。结果:26例志愿者均完成试验。受试与参比制剂抗IIa因子的E_(max),AUEC_(0~t)比值90%置信区间分别在95.36%~111.77%,83.80%~110.15%,抗Xa因子的E_(max),AUEC_(0~t)比值90%置信区间分别在101.50%~114.30%,103.57%~116.46%。上述数据满足生物等效发生标准。试验过程中有8例受试者共发生10例次不良事件。其中,受试制剂发生不良事件3例次,参比制剂发生不良事件7例次。不良事件均为轻度,未发现严重不良事件。结论:国产达肝素钠注射液与参比制剂等效,安全性和耐受性良好。
[Abstract]:Objective: to evaluate the bioequivalence and safety of single subcutaneous injection of heparin sodium into the abdominal wall of healthy adult male subjects. Open, single dose, double cycle crossover design was used to evaluate the domestic dalparin sodium injection. The subjects were randomly divided into two groups. In the first cycle, subcutaneous injection of trial preparation or reference preparation was performed. After fasting overnight for at least 10 hours, the subjects were subcutaneously injected with 0.2 mL: 5 000 IUU or reference preparation in abdominal wall, and blood samples were collected at a predetermined time point to calculate the main results by the method of .non-compartmental analysis. Pharmacokinetic parameters: the anti-Xa and IIa factors of heparin sodium were used to calculate the 90% confidence interval of the tested / reference preparations. Vital signs were taken during the test. Laboratory and electrocardiographic examination, Adverse events were recorded. All 26 subjects were included in the safety analysis set. 24 formal subjects were included in the conformance set. Results all 26 volunteers completed the test. The ratio of 90% confidence regions of the anti-IIa factor of the test and reference preparation was 90%. Between 95.3636 and 111.77 and 83.80 / 110.15, the confidence interval of 90% is 101.50 / 114.30 / 103.57 / 103.57.The above data meet the standard of bioequivalence. In the course of the experiment, there were 10 adverse events in 8 subjects. There were 3 adverse events in the tested preparations and 7 in the reference preparations. The adverse events were mild and no serious adverse events were found. Conclusion: the domestic dheparin sodium injection is equivalent to the reference preparation and has good safety and tolerance.
【作者单位】：成都军区总医院临床药学科;
【分类号】：R969

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