Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits

Abstract

Purpose: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.

Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

“…Previous studies suggest the half-life of intravitreally administered drugs may be proportional to their molecular size. 11,18 The half-life of VEGF-Trap (145 kDa) was estimated to be 4 days, similar to the estimates in our study, based on the half-life of ranibizumab (48 kDa), 14,16,19 bevacizumab (149 kDa), 13,17,20,21 and rituximab (145 kDa). 22 In addition, we could directly compare the PK parameters for ranibizumab, bevacizumab, and VEGF-Trap, because we had conducted the PK studies for these three anti-VEGF agents using the same experimental methodologies.…”

Small-animal PET demonstrates brain metabolic change after using bevacizumab in a rat model of cerebral ischemic injury

“…Ischemic neurons increase VEGF expression by activating astrocytes, and the increase usually occurs within the first few hours of ischemic stroke [36] . Since the endpoint of our study was 28 days after bevacizumab administration, its effect on VEGF was assumed to be decreased after its biological half-life of ~5 days [37,38] .…”

Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes with diabetic macular edema

“…[17][18][19] In humans, it has been well established that anti-VEGF drugs delivered within the vitreous can pass into the systemic circulation. Serum level of VEGF was demonstrated to be reduced after intravitreal bevacizumab injections in infants with retinopathy of prematurity, 8 in patients with neovascular age-related macular degeneration 9 and in patients with type 2 diabetes.…”