Testing intravitireal toxicity of bevacizumab (Avastin)

Testing intravitireal toxicity of bevacizumab (Avastin)
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DOI:
10.1097/00006982-200603000-00001
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发表时间:
2006-03-01
影响因子:
3.3
通讯作者:
Kivilcim, Muhamet
Kivilcim, Muhamet
中科院分区:
医学2区
文献类型:
--
作者:
Manzano, Roberta P. A.;Peyman, Gholam A.;Kivilcim, Muhamet

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目的:评价不同剂量贝伐单抗玻璃体内注射对兔视网膜的毒性。贝伐单抗已被美国食品和药物管理局批准用于治疗转移性结直肠癌。材料和方法:12只新西兰白化病兔用于本研究,分为4组。制备四种浓度的贝伐珠单抗:500 μ g/0.1 mL、1.0 mg/0.1 mL、2.5 mg/0.1 mL和5.0 mg/0.2 mL。在三只家兔的一只眼睛中玻璃体内注射每种浓度;将0.1 mL体积的无菌平衡盐水溶液注射到对侧眼睛中。进行裂隙灯和眼底镜检查,并观察动物2周的感染、炎症或毒性体征。在药物治疗前和第14天处死动物前进行基线视网膜电图(ERG)。结果:各组的组织学和视网膜电图检查结果均显示无视网膜毒性。然而,一些炎症细胞被发现在玻璃体中的5-mg dose.Conclusions:玻璃体内贝伐单抗没有出现毒性视网膜在白化病兔在2.5 mg的浓度。玻璃体内注射贝伐单抗治疗脉络膜新生血管和黄斑水肿的疗效应进行评估。
Purpose: To evaluate the retinal toxicity of varying doses of bevacizumab when injected intravitreally in rabbits. Bevacizumab has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer.Materials and Methods: Twelve New Zealand albino rabbits were used for this study and divided into four groups. Four concentrations of bevacizumab were prepared: 500 mu g/0.1 mL, 1.0 mg/0.1 mL, 2.5 mg/0.1 mL, and 5.0 mg/0.2 mL. Each concentration was injected intravitreally in one eye of each of three rabbits; 0.1 mL volume of sterile balanced saline solution was injected into the contralateral eyes. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, or toxicity. A baseline electroretinogram (ERG) was performed before the drug treatment and at day 14 before the animals were killed. The enucleated eyes were prepared for histologic evaluation of retinal toxicity.Results: Histologic and ERG results in all groups showed no retinal toxicity. However, some inflammatory cells were found in the vitreous at the 5-mg dose.Conclusions: Intravitreal bevacizumab did not appear toxic to the retina in albino rabbits at a concentration of 2.5 mg. Intravitreally injected bevacizumab should be evaluated for efficacy in choroidal neovascularization and macular edema.