May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Bevacizumab Pharmacokinetics Administered by Eye-Drops, Subconjunctival Injection and Intravitreal Injection in Rabbits
Author Affiliations & Notes
  • H. Nomoto
    Department of Ophthalmology, Kagawa University Faculty of Medicine, Miki, Japan
    Department of Ophthalmology, Stanford University School of Medicine, Stanford, California
  • N. Kuno
    Research and Development Center, Santen Pharmaceutical Co., Ltd., Nara, Japan
  • E. Kimura
    Research and Development Center, Santen Pharmaceutical Co., Ltd., Nara, Japan
  • K. Hirooka
    Department of Ophthalmology, Kagawa University Faculty of Medicine, Miki, Japan
  • F. Shiraga
    Department of Ophthalmology, Kagawa University Faculty of Medicine, Miki, Japan
  • Footnotes
    Commercial Relationships  H. Nomoto, None; N. Kuno, Santen Pharmaceutical Co., Ltd., E; E. Kimura, Santen Pharmaceutical Co., Ltd., E; K. Hirooka, None; F. Shiraga, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1827. doi:https://doi.org/
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    • Get Citation

      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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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