Original article
Intraocular Pharmacokinetics of Bevacizumab After a Single Intravitreal Injection in Humans

https://doi.org/10.1016/j.ajo.2008.05.036Get rights and content

Purpose

To investigate intraocular concentrations and pharmacokinetics of bevacizumab after a single intravitreal injection in humans.

Design

Prospective, noncomparative, interventional case series.

Methods

We included 30 nonvitrectomized eyes of 30 patients (age range, 43 to 93 years) diagnosed with clinically significant cataract and concurrent macular edema secondary to neovascular age-related macular degeneration, diabetic retinopathy, or retinal venous occlusion in the same eye. All patients received an intravitreal injection of 1.5 mg bevacizumab. Between one and 53 days after injection, an aqueous humor sample was obtained during elective cataract surgery. Concentrations of unbound bevacizumab in these samples were quantified by enzyme-linked immunosorbent assay.

Results

Concentration of bevacizumab in aqueous humor peaked on the first day after injection with a mean concentration (cmax) of 33.3 μg/ml (range, 16.6 to 42.5 μg/ml) and subsequently declined in a monoexponential fashion. Nonlinear regression analysis determined an elimination half-time (t1/2) of 9.82 days (R2 = 0.81). No significant differences between diagnosis subgroups were noted.

Conclusions

In human nonvitrectomized eyes, the aqueous half-life of 1.5 mg intravitreally injected bevacizumab is 9.82 days.

Section snippets

Patient Selection and Sampling

We investigated 30 eyes of 30 patients (mean age, 71.1 years; age range, 43 to 93 years; 12 females, 18 males) treated at the Department of Ophthalmology, University of Bonn. Patients agreed to participate in the study by written informed consent.

We included patients who were scheduled for cataract surgery for clinically significant lens opacification and who in addition had previously received intravitreal bevacizumab therapy for macular edema in the same eye. The macular edema was secondary

Results

Bevacizumab concentrations were measured in aqueous humor samples obtained from 30 eyes of 30 patients after intravitreal injection of 1.5 mg in the same eye (Figure 2). Bevacizumab concentration peaked on postinjection day 1, with a mean concentration (cmax) of 33.3 μg/ml (n = 5; range, 16.6 to 42.5 μg/ml). Best fit for the decline of bevacizumab concentration over time was a first-order exponential decay function. Nonlinear regression analysis of the data was performed and reached a

Discussion

To date, only a limited number of reports on the pharmacokinetics of bevacizumab in animal or human eyes has been published. This study provides, to the best of our knowledge, the first investigation on the pharmacokinetics of intraocular bevacizumab in a human case series. In our study encompassing 30 patients, the half-life of bevacizumab in aqueous humor after intravitreal delivery of 1.5 mg was 9.82 days. Our findings are in accordance with a yet unpublished study by Csaky and associates,

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