Original article
Intraocular Pharmacokinetics of Ranibizumab Following a Single Intravitreal Injection in Humans

https://doi.org/10.1016/j.ajo.2012.03.047Get rights and content

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 (cmax) of 56.1 μg/mL and an elimination half-life (t1/2) of 7.19 days with a coefficient of determination (R2) of 0.90. Correction of ranibizumab concentrations for ocular volume as calculated from axial length measurements did not alter regression analysis results significantly (t1/2, 7.15 days; R2, 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.

Section snippets

Patient Selection and Aqueous Humor Sampling

We included patients treated at the Department of Ophthalmology, University of Bonn. Inclusion criteria were planned elective cataract surgery for clinically significant lens opacification and a concurrent macular edema secondary to AMD, diabetic maculopathy, or central or branch RVO in the same eye that had been treated with a single intravitreal injection of 0.5 mg ranibizumab within 40 days before surgery. Patients with any additional intravitreal injections within 6 months before surgery or

Results

We measured aqueous humor concentration of ranibizumab in 18 eyes of 18 patients (mean age 75.1 years; age range 61–85 years; 10 female, 8 male) who had received an intravitreal injection of 0.5 mg of the drug within a period of 1 to 37 days prior to sampling (Figure 2). Macular edema was secondary to neovascular AMD in 9 patients, diabetic maculopathy in 6 patients, and central or branch RVO in 3 patients. The highest drug concentration was measured on the first day after injection (n = 2;

Discussion

Data on the ocular pharmacokinetics of ranibizumab have so far only been available from animal studies. Hence, previous predictions of pharmacokinetic properties of ranibizumab in humans as well as comparisons with other anti-VEGF agents such as bevacizumab and aflibercept had to rely on estimates of ranibizumab half-life values based on either molecular weight or animal data.9, 10, 11 Herein, we quantified ranibizumab concentration in human aqueous humor samples and provided data on the

Tim U. Krohne, MD, is a vitreoretinal specialist at the Department of Ophthalmology of University of Bonn, Germany. After graduating from University of Heidelberg, Germany, he completed his residency in Bonn in 2007. He went on to perform a postdoctoral research fellowship in cell biology at the Scripps Research Institute in La Jolla, California, before joining the faculty of University of Bonn in 2011. His research focuses on retinal cell biology, stem cells, and vitreoretinal diseases.

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    Tim U. Krohne, MD, is a vitreoretinal specialist at the Department of Ophthalmology of University of Bonn, Germany. After graduating from University of Heidelberg, Germany, he completed his residency in Bonn in 2007. He went on to perform a postdoctoral research fellowship in cell biology at the Scripps Research Institute in La Jolla, California, before joining the faculty of University of Bonn in 2011. His research focuses on retinal cell biology, stem cells, and vitreoretinal diseases.

    Carsten H. Meyer, MD, is professor of ophthalmology and a head of department at Klinik Pallas, Olten, Switzerland. He obtained his medical degree from University of Munich, Germany, and completed his residency at University of Lübeck, Germany, before pursuing a 2-year vitreoretinal fellowship at Duke Eye Center, Durham, North Carolina. He joined the University of Bonn, Germany in 2006 and became professor in 2007. His research interests include retinal imaging, chromovitrectomy, and novel therapies for AMD.

    Carsten H. Meyer is currently at Klinik Pallas, Olten, Switzerland.

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