Toxicity of high-dose intravitreal adalimumab (Humira) in the rabbit
yucloud 添加于 2012-7-11 12:52
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作 者
Manzano RPA, Peyman GA, Carvounis PE, Damico FM, Aguiar RG, Ioshimoto GL, Ventura DF, Cursino ST, Takahashi W
摘 要
PURPOSE: To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira(R)) in the rabbit eye. METHODS: Thirty New Zealand albino rabbits received intravitreous injections of 0.5 mg (6 eyes), 1.0 mg (6 eyes), 2.5 mg (6 eyes), 5 mg (6 eyes), and 10 mg (6 eyes) adalimumab. Slit lamp biomicroscopy and fundoscopy were carried out at baseline, day 7, and day 14 after intravitreous injection, whereas electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed. RESULTS: Slit lamp biomicroscopy and fundoscopy were normal in all eyes receiving doses up to 5 mg. In the 10 mg group, 3 of 6 eyes showed mild anterior chamber inflammatory reaction on day 7. Similarly, scotopic and photopic a- and b-wave ERG amplitudes at baseline and day 14 were similar in all groups up to 5 mg, but there was a significant decrease in the photopic-wave ERG response in the 10 mg group (P=0.046). Finally, histopathology demonstrated no differences among eyes receiving balanced salt solution, 0.5, 1.0, 2.5, 5.0, or 10 mg of adalimumab. CONCLUSIONS: Intravitreous adalimumab exhibited no associated ocular short-term toxicity in rabbit eyes up to the 5 mg dose. In the 10 mg group mild clinical findings and ERG amplitude reduction could reflect early toxicity. -
详细资料
- 关键词: Animals; Anterior Chamber/*drug effects/pathology; Anti-Inflammatory Agents/administration & dosage/*toxicity; Antibodies, Monoclonal, Humanized/administration & dosage/*toxicity; Dose-Response Relationship, Drug; Electroretinography/methods; Female; Inflammation/*chemically induced; Intravitreal Injections; Microscopy/methods; Ophthalmoscopy/methods; Rabbits; Time Factors
- 文献种类: Journal Article
- 期刊名称: Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
- 期刊缩写: J Ocul Pharmacol Ther
- 期卷页: 2011年 第27卷 第4期 327-331页
- 地址: Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. roberta.manzano@gmail.com
- ISBN: 1080-7683
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