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结膜下注射新型VEGF靶向抗体MIL60的眼局部药代动力学初步研究

The ocular pharmacokinetics of a new antibody (MIL60) against vascular endothelial growth factor (VEGF) following subconjunctival injection in rats
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摘要 目的初步探讨结膜下注射新型血管内皮生长因子(VEGF)靶向抗体MIL60的眼部药代动力学情况。方法取8~12周龄的健康成年新西兰大白兔20只,用30G注射器于左眼角膜缘后颞上方球结膜下注射1.25mg/0.05mlMIL60,以右眼作为对照眼。分别于给药后第5、7、14、21和28天取双眼房水、玻璃体以及外周血,通过ELISA法检测各样本的药物浓度,通过WinNonlin药代动力学软件计算主要药代动力学参数。结果兔眼结膜下注射新型VEGF靶向抗体MIL60后,在血清中和未注射眼的房水和玻璃体内均能检测到MIL60。在各个时间点,注射眼的房水和玻璃体中的MIL60浓度都高于未注射眼的房水和玻璃体内的MIL60浓度。注射眼中玻璃体的MIL60浓度高于注射眼房水中的浓度。结膜下注射MIL60后在注射眼的房水中MIL60半衰期约为10.7d,玻璃体内MIL60半衰期约为6.8d。结论MIL60结膜下注射后可进入注射眼的房水和玻璃体中并维持一定浓度,还可通过血液循环,进入未注射的对侧眼。这位MIL60将来在人眼的应用提供一定研究基础。 Objective To evaluate the ocular pharmacokinetics of a novel antibody, MIL60, targeting vascular endothelial growth factor (VEGF) after subconjunctival injection. Methods After subconjunctival injection of MIL60 in rabbits, aqueous humour, vitreous from both eyes and peripheral blood were collected of each rabbit to analyze the concentration of MIL60 with ELISA. Results After subconjunctival administration, MIL60 could penetrate into the injected eye′s anterior chamber and vitreous, and maintained at an effective concentration in the aqueous or vitreous for about 10.7 or 6.8 days. Moreover, MIL60 could be found in the uninjected eye. Conclusion After subconjunctival injection, MIL60 could maintain at a therapeutic concentration in injected eyes. The pharmacokinetics analysis of MIL60 might provide some basis and guidance for its application in humans in the near future.
作者 王群 霍焱 赵杰 黄一飞 Wang Qun;Huo Yan;Zhao Jie;Huang Yifei(The Third Medical Center of Chinese PLA General Hospital,Beijing 100039,China;The First Medical Center of Chinese PLA General Hospital,Beijing 100853 China)
出处 《中华微生物学和免疫学杂志》 CSCD 北大核心 2018年第12期938-942,共5页 Chinese Journal of Microbiology and Immunology
关键词 药代动力学 血管内皮生长因子 单克隆抗体 靶向抗体 结膜下注射 Pharmacokinetics VEGF Monoclonal antibody Targeted antibody Subconjunctival injection
作者简介 通信作者:黄一飞,Email:huangyf301@sina.com,电话:010—66936834
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