April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Vitreal Pharmacokinetics of Hesperidin Following Intravitreal Administration
Author Affiliations & Notes
  • S. Majumdar
    Department of Pharmaceutics,
    Research Institute of Pharmaceutical Sciences,
    University of Mississippi, University, Mississippi
  • R. Srirangam
    Department of Pharmaceutics,
    University of Mississippi, University, Mississippi
  • Footnotes
    Commercial Relationships  S. Majumdar, None; R. Srirangam, None.
  • Footnotes
    Support  NIH grant 5P20RR021929-02 and EY018426-02
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5956. doi:
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      S. Majumdar, R. Srirangam; Vitreal Pharmacokinetics of Hesperidin Following Intravitreal Administration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5956.

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Abstract

Purpose: : Hesperidin, a natural bioflavonoid, may act on multiple pathways associated with the initiation and progression of diabetic retinopathy and macular degeneration. The aim of this project is to determine vitreal pharmacokinetic profile of hesperidin following intravitreal administration.

Methods: : Anesthetized, white, male, New Zealand rabbits were used for thestudies. Microdialysis technique was used as a sampling technique for the determination of intravitreal pharmacokinetics (two doses). Experiments using rabbits conformed to the tenets of the Association for Research in Vision and Ophthalmology Statement on the Use of Animals in Ophthalmic and Vision Research Animal.

Results: : Vitreal pharmacokinetic parameters were calculated using noncompartmental analysis following intravitreal hesperidin administration (50 µL) at two doses 1.5 and 4.5 µg (final vitreal concentrations of 1 and 3 µg /mL). The area under the curve (AUC) was found to be 553 ± 93 and 1313 ± 229 µg.min/mL. The terminal elimination rate constant was 0.0018 ± 0.0002 and 0.00175 ± 0.0003 min-1 at the 1.5 and 4.5 µg doses, respectively with corresponding elimination half-lives of around 6.5 h. Significant difference was not observed in the mean residence time at the two doses tested and was found to be 176 ± 40 and 164 ± 42 min.

Conclusions: : Our results suggest that elimination of hesperidin from the posterior segment appears to take place at a moderate rate. The compound displayed linear pharmacokinetic profiles at the two doses tested. Further studies at additional intravitreal doses and following different routes of administration are ongoing.Acknowledgement: This project was supported by NIH grant number 5P20RR021929-02, from National Center for Research Resources, and EY018426-02, from the National Eye Institute.

Keywords: age-related macular degeneration • diabetic retinopathy 
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