Comparative safety assessments of the biosimilar APZ001 and Erbitux in pre-clinical animal models
| Autor: | Yuankeng Huang, Wang Xiaofei, Wei Yang, Caiguo Ye, Jianmin Guo, Deng Xinyu, Huiqing Liang, Junhua Rao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pentobarbital Time Factors RD1-811 Respiratory System Drug Evaluation Preclinical Cetuximab Pharmacology Kidney Kidney Function Tests Cardiovascular System Nervous System 03 medical and health sciences Mice 0302 clinical medicine Antineoplastic Agents Immunological Reference Values medicine Animals Humans Respiratory system Biosimilar Pharmaceuticals Lung business.industry Immunohistochemistry Autonomic nervous system Macaca fascicularis 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Toxicity Models Animal Female Surgery Rabbits business medicine.drug |
| Zdroj: | Acta Cirurgica Brasileira, Vol 33, Iss 8, Pp 690-702 (2018) Acta Cirúrgica Brasileira v.33 n.8 2018 Acta Cirúrgica Brasileira Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia (SBDPC) instacron:SBDPC Acta Cirurgica Brasileira, Volume: 33, Issue: 8, Pages: 690-702, Published: AUG 2018 |
| ISSN: | 0102-8650 |
| Popis: | Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux. |
| Databáze: | OpenAIRE |
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