Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF.
Drugs that prevent the binding of VEGF to its trans-membrane cognate receptors have revolutionized the treatment of the most important chorioretinal vascular disorders: exudative age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. Pegaptanib, which binds to VEGF165 and longer isoforms, ranibizumab and bevacizumab, which bind all VEGF-A isoforms, and aflibercept, which binds VEGF-A, VEGF-B, and placental growth factor, all bind VEGF165 with high affinity. The drugs have relatively long half-lives (7 to 10 days) after intravitreal depot injections and clinical durations of action that usually exceed 4 weeks. Plasma VEGF concentrations decrease after intravitreal injections of bevacizumab and aflibercept because their systemic half-lives are extended by their Fc fragments. Extensive in vitro and in vivo testing shows that the drugs prevent VEGF-mediated activation of endothelial cells while exhibiting little evidence of toxicity. Further anti-VEGF drug development is on-going.
Department of Ophthalmology, Mayo School of Medicine, 4500 San Pablo Rd, Jacksonville, 32224 FL, USA.
Michael W
MW
Stewart
D000818:Animals; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy / Q000503:physiopathology; D012170:Retinal Vein Occlusion / Q000188:drug therapy / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism*; D057135:Wet Macular Degeneration / Q000188:drug therapy / Q000503:physiopathology
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A