HIGH-MOLECULAR-WEIGHT AGGREGATES IN REPACKAGED BEVACIZUMAB
HIGH-MOLECULAR-WEIGHT AGGREGATES IN REPACKAGED BEVACIZUMAB
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DOI：
10.1097/iae.0b013e3181d50cea
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Ammar, David A.
中科院分区：
文献类型：
--
作者：
Kahook, Malik Y.;Liu, Lu;Ammar, David A.
目的：抗血管内皮生长因子药物雷珠单抗和贝伐单抗用于治疗眼部新生血管性疾病。最近有报道持续升高眼内压后，使用任何一种药物，我们假设这可能是因为高分子量aggregate.Methods：酶联免疫吸附试验，尺寸排阻色谱法，聚丙烯酰胺凝胶电泳分析重新包装的贝伐珠单抗注射器从三个外面的化合药房和样品直接从原来的小瓶。微流成像被用来检查samples.Results内的颗粒物质：所有注射器中含有统计学上相似的蛋白质量，由免疫球蛋白（IgG）的重链和轻链（聚丙烯酰胺凝胶电泳）。然而，三个复方药房批次中的两个批次溶液中的功能性IgG显著降低（酶联免疫吸附测定）。此外，最低的IgG（类似于50%）的复方药房也包含10倍的微米级颗粒物的数量，通过微流imaging.Conclusion测量：从重新包装的贝伐单抗注射器测得的IgG浓度有显着差异。随着IgG浓度的降低，存在微米级蛋白质聚集体增加的趋势。一些样本中的大颗粒物质可能导致房水流出阻塞，随后导致眼内压升高。需要进一步的研究来探索这些发现。视网膜30：887-892，2010
Purpose: The antivascular endothelial growth factor agents ranibizumab and bevacizumab are used to treat ocular neovascular diseases. There have been recent reports of sustained elevation of intraocular pressure after use of either agent, which we hypothesize could be because of high-molecular-weight aggregates.Methods: Enzyme-linked immunosorbent assay, size exclusion chromatography, and polyacrylamide gel electrophoresis were used to analyze repackaged bevacizumab syringes obtained from three outside compounding pharmacies and samples obtained directly from the original vial. Microflow imaging was used to examine particulate material within samples.Results: All syringes contained statistically similar amounts of protein, consisting of immunoglobulin (IgG) heavy and light chains (polyacrylamide gel electrophoresis). However, two of the three compounding pharmacies' batches had significantly less functional IgG in the solution (enzyme-linked immunosorbent assay). Additionally, the compounding pharmacies with the lowest IgG (similar to 50%) also contained 10-fold the number of micron-sized particulate matter as measured by microflow imaging.Conclusion: There are significant differences in IgG concentration measured from repackaged bevacizumab syringes. A trend exists for an increase in micron-sized protein aggregates with the decrease in IgG concentration. Large particulate matter within some samples may lead to obstruction of aqueous outflow and subsequent elevation in intraocular pressure. Additional studies are warranted to explore these findings. RETINA 30: 887-892, 2010