May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Vitreal Pharmacokinetics of Peptide Monoester Prodrugs of Ganciclovir Using Conscious Animal Model for Ocular Microdialysis
Author Affiliations & Notes
  • M. Minocha
    Pharmaceutical Sciences, Univrsity of Missouri Kansas City, Kansas city, Missouri
  • K. G. Janoria
    Pharmaceutical Sciences, Univrsity of Missouri Kansas City, Kansas city, Missouri
  • S. H. S. Boddu
    Pharmaceutical Sciences, Univrsity of Missouri Kansas City, Kansas city, Missouri
  • A. K. Mitra
    Pharmaceutical Sciences, Univrsity of Missouri Kansas City, Kansas city, Missouri
  • Footnotes
    Commercial Relationships  M. Minocha, None; K.G. Janoria, None; S.H.S. Boddu, None; A.K. Mitra, None.
  • Footnotes
    Support  NIH Grant R01EY09171-12 & R01EY 10659-10
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1811. doi:https://doi.org/
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    • Get Citation

      M. Minocha, K. G. Janoria, S. H. S. Boddu, A. K. Mitra; Vitreal Pharmacokinetics of Peptide Monoester Prodrugs of Ganciclovir Using Conscious Animal Model for Ocular Microdialysis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1811. doi: https://doi.org/.

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

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Abstract

Purpose: : The aim of this study is to estimate the vitreal pharmacokinetics of peptide prodrugs of ganciclovir (GCV) using conscious animal ocular microdialysis.

Methods: : New Zealand Albino male rabbits were selected as the animal model. A conscious rabbit microdialysis model with permanently implanted probes was selected as the method for investigating the vitreal pharmacokinetics of peptide monoester prodrugs of GCV, namely Valine-GCV (Val-GCV), Glycine-Valine-GCV (Gly-Val-GCV) and Valine-Valine-GCV (Val-Val-GCV) following intravitreal administration.

Results: : AUC for GCV and its prodrugs was significantly reduced in the conscious animal model compared to the anesthetized model. Half life, Mean residence time, Concentration at last time point for peptide prodrugs was also significantly less in conscious animal model. Volume of distribution, at steady state, for GCV and all three peptide prodrugs and Clearance was found to be increased in conscious relative to anesthetized animal microdialysis model. Regenerated GCV and Val GCV vitreal pharmacokinetic parameters were not affected much; this could be attributed to similar stability profile in vitreous for both models.

Conclusions: : Anesthetic combination of ketamine and xylazine may produce suppressive effect on heart and respiratory rate and may also exhibit effect on intraocular pressure, hence can impact the overall pharmacokinetic profile of a drug. Conscious animal microdialysis has been utilized in our laboratory to estimate the vitreal pharmacokinetics of GCV. This report is the first time study of assessing vitreal pharmacokinetics of a GCV prodrug using conscious animal model. More studies are needed to be performed to study the effect on carrier mediated process of peptide transporters, expressed on retina, in the presence and absence of anesthesia.

Keywords: vitreous • cytomegalovirus • retina 
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