Pharmacokinetics of Intravitreal Bevacizumab (Avastin) in Rabbits

Abstract

Purpose: : To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin) in rabbits.

Methods: : The right eye of each of 20 rabbits was injected with 1.25 mg of intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15 and 29. Bevacizumab concentrations were measured in aqueous humor, vitreous and serum using two enzyme-linked immunosorbent assays (ELISA), one of low sensitivity (5ng/ml - 0.1 µg/ml) and one of high sensitivity (10pg/ml - 5ng/ml).

Results: : Maximum vitreous (406.25 µg/ml) and aqueous humor (5.83 µg/ml) concentrations of bevacizumab in the right eye were measured 1 day after drug administration. Concentrations of >5 µg/ml bevacizumab were maintained in the vitreous 29 days after injection. A maximum serum concentration of 0.412 µg/ml was achieved 8 days after intravitreal injection and the concentration fell at 0.032 µg/ml 29 days after injection. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye reached their peak 8 days after injection, at 0.335 ng/ml, and declined to 0.2175 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak 8 days after injection, at 1.6125 ng/ml, and declined to 0.105ng/ml at 4 weeks.

Conclusions: : The maximum concentrations of bevacizumab in both vitreous and aqueous humor of right eye were reached at 1 day after injection while in the serum at 8 days after injection. Very small amounts of bevacizumab were detected in the fellow uninjected eye with the maximum concentrations measured at 8 days after injection for both the aqueous humor and vitreous.

Keywords: growth factors/growth factor receptors • immunohistochemistry