Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits

Abstract

Christos I Sinapis1,*, John G Routsias2,*, Angelos I Sinapis1,*, Dimitrios I Sinapis1,*, George D Agrogiannis3, Alkistis Pantopoulou1, Stamatis E Theocharis4, Stefanos Baltatzis5, Efstratios Patsouris3, Despoina Perrea11Laboratory for Experimental Surgery and Surgical Research 'N.S.Christeas', 2Laboratory of Pathophysiology, 3Laboratory of Pathology, 4Laboratory of Forensic Medicine and Toxicology, 5Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece *Contributed equally to the studyPurpose: To describe the pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits.Methods: The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous.Results: Maximum vitreous (406.25 µg/mL) and aqueous humor (5.83 µg/mL) concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 µg/mL) and declined to 0.032 µg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL) and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL) and declined (to 0.11 ng/mL) at 4 weeks.Conclusion: The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye.Keywords: bevacizumab, pharmacokinetics, rabbits, intravitreal