Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

BACKGROUND: Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data. METHODS: Twenty-two (22 eyes) were included in this study, and divided into four groups: eight patients received topical bevacizumab and aqueous samples were obtained 1 hour later during cataract extraction surgery (group 1), eight patients received topical bevacizumab and vitreous samples were obtained 1 day later during pars-plana vitrectomy (PPV) (group 2), three patients received intravitreal bevacizumab and vitreous samples were obtained during PPV (group 3). Vitreous samples from three patients who received no bevacizumab served as controls (group 4). All samples underwent enzyme-linked immunosorbent assay to detect bevacizumab. RESULTS: No bevacizumab was detected in the aqueous or vitreous of any topically treated eyes. The mean vitreal half-life for intravitreally injected bevacizumab was 4.9 days in four non-vitrectomized eyes and 0.66 days in one previously vitrectomized eye. CONCLUSIONS: Topically administered bevacizumab does not penetrate the cornea into the anterior chamber and vitreous cavity, indicating that topical use for treating corneal neovascularization has minimal risk of intraocular penetration and adverse events related to intraocular vascular endothelial growth factor inhibition. The half-life following intravitreal bevacizumab injection measured in this study is comparable to that of previous reports, and includes the first demonstration of a significantly reduced half-life following intravitreal injection in a previously vitrectomized eye.