title: Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD.
abstract: BACKGROUND
  Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking.
  
  
  METHODS
  Fifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections.
  
  
  RESULTS
  Following the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) VEGF levels with ranibizumab were largely unchanged, with mean trough level of 14.4 pg/mL compared with baseline of 17 pg/mL.
  
  
  CONCLUSIONS
  There are notable differences in systemic pharmacokinetics and pharmacodynamics among anti-VEGF treatments after intravitreal administration. All three agents rapidly moved into the bloodstream, but ranibizumab very quickly cleared, whereas bevacizumab and aflibercept demonstrated greater systemic exposure and produced a marked reduction in plasma free VEGF.
  
  
  BACKGROUND
  NCT02118831.
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Avery
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Alessandro A
authors.initials: AA
authors.lastname: Castellarin
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Steinle
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Dilsher S
authors.initials: DS
authors.lastname: Dhoot
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Dante Joseph
authors.initials: DJ
authors.lastname: Pieramici
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: See
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Couvillion
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Ma'an A
authors.initials: MA
authors.lastname: Nasir
authors.affiliation: California Retina Consultants, Santa Barbara, California, USA.
authors.forename: Melvin D
authors.initials: MD
authors.lastname: Rabena
authors.affiliation: Genentech Inc., South San Francisco, California, USA.
authors.forename: Kha
authors.initials: K
authors.lastname: Le
authors.affiliation: Genentech Inc., South San Francisco, California, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Maia
authors.affiliation: Genentech Inc., South San Francisco, California, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Visich
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D001682:Biological Availability; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006207:Half-Life; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D011446:Prospective Studies; D000069579:Ranibizumab; D040262:Receptors, Vascular Endothelial Growth Factor / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood; D014822:Vitreous Body / Q000378:metabolism; D057135:Wet Macular Degeneration / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Retina