Retina. 2017 Oct;37(10):1847-1858. doi: 10.1097/IAE.0000000000001493.


Purpose: To evaluate the systemic pharmacokinetics (PKs) of aflibercept, bevacizumab, and ranibizumab in patients with neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO).

Methods: Prospective, open-label, nonrandomized clinical trial of patients with AMD, DME, or RVO who were antivascular endothelial growth factor (VEGF) naïve or had not received anti-VEGF for ≥4 months. Patients received 3 monthly intravitreal injections of aflibercept 2.0 mg, bevacizumab 1.25 mg, or ranibizumab (0.5 mg for AMD/RVO, 0.3 mg for DME). The main outcome measures were serum PKs and plasma free-VEGF concentrations after the first and third injections.

Results: A total of 151 patients were included. In AMD/DME/RVO, systemic exposure to each drug was highest with bevacizumab, then aflibercept, and lowest with ranibizumab. Ranibizumab cleared from the bloodstream more quickly than bevacizumab or aflibercept. Aflibercept treatment resulted in the greatest reductions in plasma free-VEGF relative to baseline levels, whereas ranibizumab treatment resulted in the smallest decreases in plasma free-VEGF.

Conclusion: The three anti-VEGF treatments examined in this analysis demonstrated notable differences in systemic PKs. Generally, the reduction in plasma free-VEGF levels correlated with elevated levels of circulating anti-VEGF agents, with the reduction in free-VEGF levels greatest with aflibercept and least with ranibizumab.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacokinetics
  • Bevacizumab / administration & dosage
  • Bevacizumab / pharmacokinetics*
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / drug therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Macular Edema / blood
  • Macular Edema / drug therapy*
  • Macular Edema / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Ranibizumab / administration & dosage
  • Ranibizumab / pharmacokinetics*
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacokinetics*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / blood
  • Wet Macular Degeneration / blood
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*


  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor
  • Ranibizumab