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玻璃体切除眼与未行玻璃体切除眼玻璃体内抗血管内皮生长因子药物的药代动力学

Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes.

作者信息

Edington Magdalena, Connolly Julie, Chong Ngaihang Victor

机构信息

a Department of Ophthalmology , University of Oxford , Oxford , UK.

b Department of Ophthalmology , Tennent Institute of Ophthalmology , Glasgow , UK.

出版信息

Expert Opin Drug Metab Toxicol. 2017 Dec;13(12):1217-1224. doi: 10.1080/17425255.2017.1404987. Epub 2017 Nov 15.

Abstract

The review aims to discuss effects of vitrectomy on pharmacokinetics of anti-vascular endothelial growth factor (anti-VEGF) agents, and attempt to provide treatment guidance. Areas covered: An Embase search was conducted using the terms 'anti-VEGF', 'pegaptanib', 'ranibizumab', 'bevacizumab', 'aflibercept', 'pharmacokinetics', 'half-life', 'clearance', 'metabolism', 'vitrectomy', 'vitrectomized'. Published data regarding the pharmacokinetic properties of the above drugs and the effect of vitrectomy in animal and human eyes was reviewed. Expert opinion: There are limited studies on the effect of vitrectomy on pharmacokinetic properties of anti-VEGF drugs in human eyes. Most animal models indicate that intravitreal drugs have reduced half-lives and increased clearance in vitrectomized eyes. More studies, with carefully selected design, are required to explore this further. However, considering existing evidence, it is important to consider vitreous and lens status when monitoring and treating patients. Authors recommend fixed monthly dosing, with low threshold for increasing frequency of injection even to 2-weekly if required, as well as close monitoring of patients to establish individual response. There may be an increased role for slow-release steroid implants in vitrectomized eyes with DME or RVO. Longer acting substances currently under development such as brolucizumab or abicipar pegol, may become the treatment of choice in the future.

摘要

本综述旨在探讨玻璃体切除术对抗血管内皮生长因子(抗VEGF)药物药代动力学的影响,并尝试提供治疗指导。涵盖领域:使用“抗VEGF”“培加尼布”“雷珠单抗”“贝伐单抗”“阿柏西普”“药代动力学”“半衰期”“清除率”“代谢”“玻璃体切除术”“接受玻璃体切除术的”等术语在Embase数据库进行检索。对已发表的关于上述药物药代动力学特性以及玻璃体切除术对动物和人眼影响的数据进行了综述。专家观点:关于玻璃体切除术对人眼抗VEGF药物药代动力学特性影响的研究有限。大多数动物模型表明,玻璃体腔内注射药物在接受玻璃体切除术的眼中半衰期缩短、清除率增加。需要开展更多精心设计的研究以进一步探索这一问题。然而,考虑到现有证据,在对患者进行监测和治疗时,考虑玻璃体和晶状体状态很重要。作者建议采用固定的每月给药方案,若有必要,即使增加至每2周注射一次的注射频率阈值也较低,同时密切监测患者以确定个体反应。对于患有糖尿病性黄斑水肿(DME)或视网膜静脉阻塞(RVO)的接受玻璃体切除术的眼,缓释类固醇植入物可能会发挥更大作用。目前正在研发的作用时间更长的药物,如布罗利珠单抗或阿比西帕聚乙二醇,未来可能会成为治疗的首选。

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