Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver, Aurora, Colorado 80045, USA.
Retina. 2010 Jun;30(6):887-92. doi: 10.1097/IAE.0b013e3181d50cea.
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.
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.
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 ( approximately 50%) also contained 10-fold the number of micron-sized particulate matter as measured by microflow imaging.
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.
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疾病。最近有报道称，两种药物使用后眼压持续升高，我们推测这可能是由于高分子量聚集物。
采用酶联免疫吸附试验、分子筛层析和聚丙烯酰胺凝胶电泳分析从三家外部配制药房获得的重新包装的贝伐单抗注射器和直接从原始小瓶获得的样品。微流成像用于检查样品中的颗粒物质。
所有注射器中均含有统计学上相似量的蛋白质，包括免疫球蛋白（IgG）重链和轻链（聚丙烯酰胺凝胶电泳）。然而，三家配制药房中的两批药物溶液中的功能性 IgG 明显减少（酶联免疫吸附试验）。此外，用微流成像测量，IgG 含量最低（约 50%）的两家配制药房的药物中含有 10 倍数量的微米级颗粒物质。
从重新包装的贝伐单抗注射器中测量的 IgG 浓度存在显著差异。随着 IgG 浓度的降低，存在微米级蛋白聚集物增加的趋势。一些样品中的大颗粒物质可能导致房水流出受阻，随后眼压升高。需要进一步的研究来探讨这些发现。
