Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF

Expert Rev Clin Pharmacol. 2014 Mar;7(2):167-80. doi: 10.1586/17512433.2014.884458. Epub 2014 Feb 3.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / physiopathology
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Humans
  • Intravitreal Injections
  • Macular Edema / drug therapy
  • Macular Edema / physiopathology
  • Retinal Vein Occlusion / drug therapy
  • Retinal Vein Occlusion / physiopathology
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / metabolism*
  • Wet Macular Degeneration / drug therapy
  • Wet Macular Degeneration / physiopathology


  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A