Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans

Am J Ophthalmol. 2012 Oct;154(4):682-686.e2. doi: 10.1016/j.ajo.2012.03.047. Epub 2012 Jul 19.

Abstract

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 μg/mL) and subsequently declined in a mono-exponential fashion. Nonlinear regression analysis determined an initial peak concentration (c(max)) of 56.1 μg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / pharmacokinetics*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Aqueous Humor / metabolism*
  • Axial Length, Eye
  • Biological Availability
  • Biometry
  • Cataract / etiology
  • Cataract / metabolism
  • Cataract Extraction
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Half-Life
  • Humans
  • Intravitreal Injections
  • Macular Degeneration / complications
  • Macular Degeneration / drug therapy
  • Macular Degeneration / metabolism
  • Macular Edema / drug therapy
  • Macular Edema / etiology
  • Macular Edema / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Ranibizumab
  • Retinal Vein Occlusion / complications
  • Retinal Vein Occlusion / drug therapy
  • Retinal Vein Occlusion / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Ranibizumab