Influence of heterogeneous drugs on complement activation and its clinical significance
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摘要: 目的 补体活性测量被评价为药物一致性和药物免疫毒性的检测指标之一,因此,建立一个敏感、可靠、标准、快捷的药物理化性质与免疫补体激活CARPA的评价标准,用于界定药物对补体活化作用的影响。 方法 收集宜昌市中心人民医院中医免疫科和肾病综合科送检的健康者血清140例,加入免疫球蛋白Ig G和zymosan A刺激剂作为标准阳性对照,把经典途径的特异性因子C4d、C5a、SC5b-9和替代途径特异性因子Bb作为检测指标,建立药物对补体活性影响的体外评价标准,并确定为评价模型。应用该评价标准,以异源型的两性霉素B及注射用的伏立康唑为研究对象,对本药物免疫毒性、仿制与市售制剂药物一致性建立一个初步评价。 结果 Ambisome、ABCD组和d-AmB组处方中,Ambisome和d-AmB激活补体的能力较强,其中Ambisome能够同时激活CP和AP两种途径,而d-AmB仅能激活AP途径。测量到市售的RLD1、RLD2和RLD3两性霉素B脂质体制剂血清中SC5b-9的含量基本一致,均值为(22.16±0.63)μg/ml、而C5a的含量波动幅度较大,平均值为(571.32±106.12)ng/ml,自制的Test1和Test2两性霉素B脂质体制剂在血清中SC5b-9和C5a的含量与市售制剂的均值存在差异性。 结论 初步建立了异源型药物对免疫补体活性调控的体外评价标准。Abstract: Objective Complement activity test is commonly used to evaluate the consistency and immune toxicity of drugs. The aim of this study is to establish a sensitive, reliable and fast evaluation criterion for the physical and chemical properties of drugs and complement activation-related pseudo-allergy (CARPA). Methods The standard reaction serum was prepared by pooling sera collected from 140 healthy blood donors in our hospital; a standard positive control was prepared by incubation with a heat-agglutinated IgG and zymosan A; SC5b-9, C5a, C4d and Bb were chosen as the test targets and evaluation criteria of the results was defined, all of these constituted the in-vitro model. By using this evaluation criterion, heterogeneous Amphotericin B and Voriconazole injection were employed to evaluate primarily their immune toxicity, imitation and consistent with commercially drugs. Results The ability of AmBisome and d-AmB activating complement was strong in the prescription of AmB liposome (Ambisome), homemade AmB cholesterol sodium sulfate complex (ABCD) group and injectable amphotericin B (d-AmB) groups. Among them, AmBisome can activate both classical pathways (CP) and alternative pathways (AP), but d-AmB can only activate the alternative pathways (AP). The level of SC5b-9 in the RLD1, RLD2 and RLD3 amphotericin B liposome of serum was the same, the average level was (22.16±0.63)μg/ml; however, the fluctuation in the level of C5a was high, average was (571.32±106.12)ng/ml. The significant difference in the levels of SC5b-9 and C5a was found between the homemade Test1 and Test2 amphotericin B liposome and the RLD1, RLD2 and RLD3 amphotericin B liposome of serum. Conclusion The evaluation criterion in vitro for immune complement activity regulation was preliminarily established by heterologous drugs.
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Key words:
- Complement activation /
- Classical pathway /
- Alternative pathway /
- Amphotericin B /
- Voriconazole
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