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国产那屈肝素钙注射液在中国健康受试者中的生物等效性及安全性研究
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| 篇名： | 国产那屈肝素钙注射液在中国健康受试者中的生物等效性及安全性研究 |
| TITLE： | Bioequivalence and safety evaluation of domestic Nadroparin calcium injection in Chinese healthy volunteers |
| 摘要： | 目的 评价健康成年受试者皮下注射两种那屈肝素钙注射液的生物等效性和安全性。方法共纳入成年健康受试者24例，按区组随机化法以1∶1分配到TR（受试制剂-参比制剂）组和RT（参比制剂-受试制剂）组。采用随机、开放、单剂量、双周期交叉设计，两组受试者均于每个周期的第1天空腹皮下注射受试制剂或参比制剂6150AⅩaIU，第2周期交叉给药，清洗期为7d。于给药前后不同时间点采集血样，采用发色底物法测定人血浆样品中各制剂的抗凝血因子Ⅹa（Anti-Ⅹa）活性和抗凝血因子Ⅱa（Anti-Ⅱa）活性，按非房室模型计算药效动力学参数并进行生物等效性评价；同时记录受试者不良事件发生情况。结果给药后，受试制剂和参比制剂Anti-Ⅹa活性的半衰期（t1/2）分别为（4.87±1.06）、（4.03±1.00）h，达峰时间（tmax）分别为4.50（2.00，8.00）、5.50（2.50，8.00）h，Anti-Ⅹa活性最大值（Anti-Ⅹamax）分别为（0.66±0.12）、（0.56±0.11）IU/mL；受试制剂和参比制剂Anti-Ⅱa活性的t1/2分别为（3.64±1.60）、（5.74±7.23）h，tmax分别为4.00（2.50，8.00）、4.00（2.00，8.00）h，Anti-Ⅱa活性最大值均为（0.10±0.03）IU/mL；两制剂Anti-Ⅹamax、活性-时间曲线下面积（AUEC0－t、AUEC0－∞）几何均值比的90％置信区间分别为110.98％～123.50％、112.11％～121.24％、111.57％～120.00％。试验过程中，有14例受试者发生19例次轻度不良事件，其中血肿、紫癜、斑丘疹可能与药物有关；未见严重的不良事件发生。结论国产那屈肝素钙注射液与参比制剂生物等效，两药的安全性均较好。 |
| ABSTRACT： | OBJECTIVE To evaluate the bioequivalence and safety of two k inds of Nadroparin calcium injection in healthy Chinese volunteers by subcutaneous injection. METHODS According to the block randomization method ，24 Chinese healthy adult volunteers were included and divided into TR （test preparation-reference preparation ）group and RT （reference preparation-test preparation）group at a ratio of 1∶1. A randomized ，open-labelled，single-dose and two-cycle crossover study was designed ，the fasting subjects of two groups were given test or reference preparation 6 150 AⅩaIU subcutaneously on the first day of each cycle and exchanged in the second cycle ，and the wash-out period was 7 days. The blood samples were collected at different time points before and after administration. The activity of anti-coagulant factor Ⅹa（Anti-Ⅹa）and Anti- Ⅱa in human plasma were determined by chromogenic substrate method ，and the pharmacodynamic parameters were calculated according to the non-atrioventricular model and the bioequivalence was evaluated. The occurrence of adverse events （AEs）was recorded. RESULTS After administration ，the main pharmacodynamic parameters for Anti- Ⅹa activity of test preparation and reference preparation were as follows ：t1/2 were（4.87±1.06） and（4.03±1.00）h，tmax were 4.50（2.00，8.00）and 5.50（2.50，8.00）h，Anti-Ⅹamax were（0.66±0.12）and（0.56±0.11）IU/mL；main pharmacodynamic parameters of Anti- Ⅱa activity of two preparations were as follows ：t1/2 were（3.64±1.60）and（5.74±7.23）h，tmax were 4.00（2.50，8.00）and 4.00（2.00，8.00）h，Anti-Ⅱamax were both （0.10±0.03）IU/mL. The values of 90％confidence interval of geometric mean ratio of Anti- Ⅹamax，AUEC0－t and AUEC 0－∞ were 110.98％-123.50％，112.11％-121.24％and 111.57％-120.00％， respectively. During experiment ，14 subjects reported 19 cases of mild AEs ，among which hematoma ，purpura and maculopapular rash may be related to drugs ；no serious AEs were observed. CONCLUSIONS The domestic Nadroparin calcium injection is bioequivalent to the reference preparation ，and both of them show good safety. |
| 期刊： | 2022年第33卷第16期 |
| 作者： | 李洁，宋恒文，杨能，邵志超，钱春艳 |
| AUTHORS： | LI Jie，SONG Hengwen ，YANG Neng，SHAO Zhichao ，QIAN Chunyan |
| 关键字： | 那屈肝素钙注射液；生物等效性；安全性评价 |
| KEYWORDS： | Nadroparin calcium injection ；bioequivalence； |
| 阅读数： | 345 次 |
| 本月下载数： | 9 次 |
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