Abstract
Purpose: :
To investigate the pharmacokinetics of bevacizumab after various topical administrations of commercial Avastin<sup>®</sup>.
Methods: :
Pigmented rabbits received Avastin in one eye (right eye) by topical eye-drops (50µL-6times/day for 7days), single subconjunctival injection (50µL/eye) or single intravitreal injection (50µL/eye). At predetermined intervals (1 week, 2 weeks, 4 weeks and 12 weeks after administrations), rabbits were euthanized, enucleated and blood samples collected. Bevacizumab concentrations in plasma aqueous humor, vitreous, iris/ciliary body, and retina/choroids in treated and fellow eyes were determined by sandwich ELISA for human IgG (primary antibody; Rabbit anti-human IgG (H+L), secondary antibody; HRP anti-human IgG (H+L)). To examine localization of bevacizumab in retina, retinas were prepared for immunohistochemical staining with antibody to human IgG in selected samples.
Results: :
In the eyes that received bevacizmab by intravitreal injection, the mean concentrations of bevacizumab in the aqueous humor, iris/ciliary body, retina/choroids at 1 week were 27.6 µg/mL, 1295.5µg/g, 308.6 µg/g, respectively. In fellow eyes, low levels of bevacizumab were detected in the iris/choroids and retina/choroids, but scarcely in the vitreous. Mean plasma concentration of bevacizmab was 2.1µg/mL at 1 week. In the treated and fellow eyes of rabbits that received bevacizmab by subconjunctival injection and eye-drops, very low levels of bevacizumab were also detected in iris/ciliary body and retina/choroid, but scarcely in the vitreous. One week after intravitreal injection, strong staining of the inner limiting membrane and blood vessels were observed. Bevacizumab was also found in Müller cells.
Conclusions: :
Bevacizumab could be distributed in the fellow eyes by not only intravitreal injection but also sunconjunctival injection and eye-drops. Since bevacizumab was detected in plasma, but not in the vitreous, it was thought that bevacizumab in the fellow eyes was localized via systemic circulation.
Keywords: drug toxicity/drug effects • retina