title: A model of the ocular pharmacokinetics involved in the therapy of neovascular age-related macular degeneration with ranibizumab.
abstract: BACKGROUND
  To develop a model of the pharmacokinetics of vascular endothelial growth factor (VEGF-A) determined in samples of aqueous humour from patients with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis).
  
  
  METHODS
  Post hoc analysis of data from 31 eyes of 31 patients with AMD treated with ranibizumab gathered in a non-randomised, prospective clinical study. VEGF-A concentrations were measured in 440 aqueous humour samples by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA).
  
  
  RESULTS
  The kinetics of recovery of VEGF-A from suppression by ranibizumab were well described by a simple model: VEGF-A is produced at a constant individual rate; VEGF-A and ranibizumab disperse rapidly within the vitreous chamber and bind with a known affinity; both are eliminated at identical rates from the vitreous chamber in a constant but individual flow into the anterior chamber, and are finally cleared by draining into the peripheral circulation. Average rates of VEGF-A production were predicted to be 5.8 fmol/day (range: 2.7-10.1 fmol), and elimination half-times predicted to be 3.5 days (range: 2.3-5.5 days). The duration of complete VEGF-A suppression in the aqueous humour averaged 41 days (range: 28-67 days).
  
  
  CONCLUSIONS
  The ocular pharmacokinetics of VEGF-A and ranibizumab have been linked for the first time in a simple and plausible model which suggests that it might be possible to anticipate individual VEGF-A suppression times.
  
  
  BACKGROUND
  NCT01213667.
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Saunders
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Muether
authors.affiliation: Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069579:Ranibizumab / Q000493:pharmacokinetics*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab
keywords: Aqueous humour; Retina; Treatment Medical