May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Antiviral Efficacy of Dipeptide Ganciclovir and Acyclovir Prodrugs, Val–Val–Ganciclovir (VVGCV) and Gly –Val–Acyclovir (GVACV), Against HSV–1 Corneal Epithelial Keratitis in the Rabbit
Author Affiliations & Notes
  • M. Itahashi
    Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA
  • S.G. Trahan
    Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA
  • B.S. Anand
    School of Pharmacy, University of Missouri–Kansas City, Kansas City, MO
  • H.W. Thompson
    Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA
  • S. Majumdar
    School of Pharmacy, University of Missouri–Kansas City, Kansas City, MO
  • Y.E. Nashed
    School of Pharmacy, University of Missouri–Kansas City, Kansas City, MO
  • A.K. Mitra
    School of Pharmacy, University of Missouri–Kansas City, Kansas City, MO
  • J.M. Hill
    Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA
  • Footnotes
    Commercial Relationships  M. Itahashi, None; S.G. Trahan, None; B.S. Anand, GlaxoSmithKline F; H.W. Thompson, None; S. Majumdar, GlaxoSmithKline F; Y.E. Nashed, GlaxoSmithKline F; A.K. Mitra, GlaxoSmithKline F, P; J.M. Hill, None.
  • Footnotes
    Support  EY09171,EY10659,EY06311,EY02377,RPB
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 117. doi:
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      M. Itahashi, S.G. Trahan, B.S. Anand, H.W. Thompson, S. Majumdar, Y.E. Nashed, A.K. Mitra, J.M. Hill; Antiviral Efficacy of Dipeptide Ganciclovir and Acyclovir Prodrugs, Val–Val–Ganciclovir (VVGCV) and Gly –Val–Acyclovir (GVACV), Against HSV–1 Corneal Epithelial Keratitis in the Rabbit . Invest. Ophthalmol. Vis. Sci. 2004;45(13):117.

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

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Abstract

Abstract: : Purpose:To determine the antiviral efficacy of the dipeptide prodrugs of ganciclovir (GCV) and acyclovir (ACV), VVGCV and GVACV, in HSV–1–specific corneal epithelial keratitis on the New Zealand White (NZW) rabbit. Methods:NZW rabbits (32) were topically inoculated with HSV–1 strain McKrae onto both scarified corneas and randomized into 4 balanced groups (8 rabbits/ group). At 3 days post–inoculation (PI Day 3), VVGCV, GVACV, trifluorothymidine (TFT), and water solutions were topically administered to the rabbit eyes 5 times per day between 9 AM and 5 PM for 5 consecutive days. All drugs were prepared at 1% wt/vol. Corneal epithelial keratitis, chemosis, and conjunctivitis were assessed and scored in each eye via slit lamp examination (SLE) from PI Days 3–7. On PI Day 7 (post–treatment day 5), aqueous humor was collected from each rabbit approximately one hour after the day’s final topical drop administration for determination of antiviral concentration. Results:SLE scores, mean and standard deviation were determined for five days. We found that VVGCV and GVACV treatment displayed antiviral effectiveness against HSV–1 in the NZW rabbit ocular model similar to TFT. Interestingly, the VVGCV treatment cessation did not result in a "rebound" of SLE scores/epithelial keratitis, as was seen at the termination of TFT, GVACV and water. Antiviral drug concentration in the aqueous humor will be reported. Conclusions:These results show that VVGCV and GVACV are highly effective antiviral prodrugs in treating HSV–1 rabbit epithelial keratitis, similar to TFT. VVGCV may have a longer half–life, thus preventing the aforementioned "rebound" seen with the TFT, GVACV and water treatment groups. Therefore, these two prodrugs could prove to be promising treatments for HSV–1 keratitis when TFT cannot be utilized.

Keywords: herpes simplex virus • antiviral drugs • cornea: epithelium 
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