硫酸阿米卡星注射剂对凝血功能的影响及溶血试验研究

摘要：目的 研究硫酸阿米卡星注射剂对凝血功能及溶血的影响。方法 采用不同浓度的硫酸阿米卡星加入到正常血浆中，制备含药血浆，分别测定正常血浆及含药血浆中的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)的含量。分别用光度法及目视法比较两种溶剂中，硫酸阿米卡星注射剂引起的溶血反应。结果 测定结果表明，阿米卡星浓度为128 mg/L时(为说明书最大血药浓度的2倍)，与正常血浆对照相比，0h的APTT值均有显著性增加(P＜0.01)。加入药物作用2和3 h后，样品浓度为64和32 mg/L时，APTT结果均有显著性差异(P＜0.05或P＜0.01)。作用3h后，注射用硫酸阿米卡星在浓度为16 mg/L时，APTT结果依然有显著性差异(P＜0.01)。APTT值与阿米卡星浓度呈线性相关(R2＞0.95)。用0.9%氯化钠注射液作为稀释液达到5 mg/mL临床配伍浓度时，存在溶血的安全隐患。而以5%葡萄糖注射液为稀释液的供试品溶液达到10、5和2.5 mg/mL临床配伍浓度时，9家企业22批次产品溶血率均小于5%，均未发生溶血现象。结论 在体外实验中，硫酸阿米卡星注射剂可以影响血凝检测结果。硫酸阿米卡星注射剂存在溶血安全隐患，临床配伍时，选用5%葡萄糖注射液为稀释液可能会更安全。

Study on the influence of amikacin sulfate injection on coagulation function and the hemolytic test

Abstrct Objective To study the effects of amikacin sulfate injection on blood coagulation function and the hemolytic test. Methods Different concentrations of amikacin sulfate injection were added into the plasma to prepare test solutions. PT, APTT, TT, and FIB in plasma on different times were detected respectively. The results of the hemolytic tests in two solvents were compared by spectrophotometry and the visual method. Results At the concentration of 128 mg/L, the value of APTT increased significantly(P＜0.01) compared with control plasma at zero hour. At the concentration of 64 mg/L and 32 mg/L after the drug was added into the plasma for 2 and 3 hours, the value of APTT increased significantly (P＜0.05 and P＜0.01). After the drug was added in the plasma for 3 hours, the value of APTT increased significantly(P＜0.01) at the concentration of 16 mg/L. There is a liner relation between the value of APTT and the concentration of amikacin sulfate injection(R2＞0.95). At or above the concentration of 5 mg/mL when samples were diluted in 0.9% sulfate chloride injection, hemolysis was detected by the spectrophotometry method at 3 hours and there existed security risks. The hemolytic rates of 22 batches of samples from nine companies were below 5% when diluted in 5% glucose injection to the concentration of 10, 5 and 2.5 mg/mL by the spectrophotometry method. Conclusion Cogulation analyzing results could be affected by amikacin sulfate injectionin vitro. Potential safety risks of hemolysis exist in clinical use of amikacin sulfate injection, but it will be better by using 5% glucose injection as