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A model of the ocular pharmacokinetics involved in the therapy of neovascular age-related macular degeneration with ranibizumab
  1. Derek J Saunders,
  2. Philipp S Muether,
  3. Sascha Fauser
  1. Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany
  1. Correspondence to Dr Sascha Fauser, Department of Ophthalmology, University Hospital of Cologne, Kerpener Str. 62, Cologne 50924, Germany; sascha.fauser{at}


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.

Clinical trial number NCT01213667.

  • Aqueous humour
  • Treatment Medical
  • Retina

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