Intraocular Pharmacokinetics of Ranibizumab Following a Single Intravitreal Injection in Humans

PURPOSE: To investigate intraocular concentrations and pharmacokinetics of ranibizumab after a single intravitreal injection in humans. DESIGN: Prospective, noncomparative, interventional case series. METHODS: We included 18 nonvitrectomized eyes of 18 patients (age range, 61-85 years) that were diagnosed with both clinically significant cataract and macular edema secondary to either exudative age-related macular degeneration, diabetic maculopathy, or retinal vein occlusion. Each eye received a single intravitreal injection of 0.5 mg ranibizumab. An aqueous humor sample was obtained during cataract surgery between 1 and 37 days after injection. Concentrations of unbound ranibizumab in these samples were quantified by enzyme-linked immunosorbent assay. RESULTS: Ranibizumab concentration in aqueous humor peaked the first day after injection (range, 36.9-66.1 mu g/mL) and subsequently declined in a mono-exponential fashion. Nonlinear regression analysis determined an initial peak concentration (c(max)) of 56.1 mu g/mL and an elimination half-life (t(1/2)) of 7.19 days with a coefficient of determination (R-2) of 0.90. Correction of ranibizumab concentrations for ocular volume as calculated from axial length measurements did not alter regression analysis results significantly (t(1/2), 7.15 days; R-2, 0.89). CONCLUSIONS: In human nonvitrectomized eyes, the aqueous half-life of 0.5 mg intravitreally injected ranibizumab is 7.19 days, slightly shorter than the half-life of 9.82 days previously determined for bevacizumab by comparable methods. (Am J Ophthalmol 2012;154: 682-686. (C) 2012 by Elsevier Inc. All rights reserved.)