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H. Nomoto, N. Kuno, E. Kimura, K. Hirooka, F. Shiraga; Bevacizumab Pharmacokinetics Administered by Eye-Drops, Subconjunctival Injection and Intravitreal Injection in Rabbits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1827.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the pharmacokinetics of bevacizumab after various topical administrations of commercial Avastin<sup>®</sup>.
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.
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.
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.
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