与创新产品相比，九种阿米卡星仿制药在中性粒细胞减少小鼠大腿感染模型中的药效学研究。
Pharmacodynamics of nine generic products of amikacin compared with the innovator in the neutropenic mouse thigh infection model.
作者信息
Zuluaga Andres F, Rodriguez Carlos A, Agudelo Maria, Vesga Omar
机构信息
GRIPE [Grupo Investigador de Problemas en Enfermedades infecciosas], Universidad de Antioquia, Calle 70 No. 52-21, Medellín, Colombia.
Department of Pharmacology and Toxicology at Medical School, Universidad de Antioquia, Calle 70 No. 52-21, Medellín, Colombia.
出版信息
BMC Res Notes. 2015 Oct 7;8:546. doi: 10.1186/s13104-015-1507-z.
BACKGROUND
Previously, we validated the mouse thigh infection model to test the therapeutic equivalence of generic antibiotic products. Here, our aim was to compare the in vivo efficacy of amikacin products in clinical use in Colombia using this animal model.
RESULTS
All except one generic product had the same in vitro potency, judging by the lack of differences on MIC and MBC compared with the innovator. However, eight of nine generic products failed in the neutropenic mouse thigh infection model to achieve the innovator's maximum effect (E max ≤ 5.65 for the generics vs. 6.58 log10 CFU/g for the innovator) against Escherichia coli SIG-1, after subcutaneous treatment every 6 h with doses ranging from 1.5 to 3072 mg/kg per day.
CONCLUSION
As we demonstrated previously with other antibiotics such as vancomycin, gentamicin and oxacillin, the generic products of amikacin failed the in vivo efficacy testing. The therapeutic equivalence should be assessed in vivo before clinical approval of generic products.
背景
此前，我们验证了小鼠大腿感染模型以测试仿制药抗生素产品的治疗等效性。在此，我们的目的是使用该动物模型比较哥伦比亚临床使用的阿米卡星产品的体内疗效。
结果
除一种仿制药产品外，所有产品的体外效力相同，与创新药相比，其 MIC 和 MBC 无差异。然而，在每 6 小时皮下注射剂量范围为 1.5 至 3072 mg/kg/天的情况下，九种仿制药产品中有八种在中性粒细胞减少小鼠大腿感染模型中未能达到创新药针对大肠杆菌 SIG-1 的最大效应（仿制药的 E max≤5.65，而创新药为 6.58 log10 CFU/g）。
结论
正如我们之前用其他抗生素如万古霉素、庆大霉素和苯唑西林所证明的那样，阿米卡星的仿制药产品未能通过体内疗效测试。在仿制药产品临床批准之前，应在体内评估其治疗等效性。
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