Evaluation of 1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-ethyluracil in a rabbit model of herpetic keratitis Journal Article

  


Authors: Trousdale, M. D.; Law, J. L.; Yarber, F. A.; Watanabe, K. A.; Fox, J. J.
Article Title: Evaluation of 1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-ethyluracil in a rabbit model of herpetic keratitis
Abstract: The nucleoside analog 1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-ethyluracil (FEAU) was tested in a rabbit model of acute herpetic keratitis and its effectiveness compared with that of acyclovir (ACV). FEAU or ACV was applied topically 3 times daily, beginning 3 days post-HSV-1 inoculation and continued for a period of 7 days. FEAU at a concentration of 1% (w/v) or 3% ACV resulted in significant lessening of the severity of corneal lesions, conjunctivitis, iritis, and corneal clouding at 24 to 48 h after beginning chemotherapy. No toxic reaction was observed in any rabbit eyes treated with either FEAU or ACV. The duration of virus shedding into tear film and colonization of the trigeminal ganglia, however, were not reduced by either FEAU or ACV treatment begun 3 days post-inoculation. Fifty percent effective dose (ED50) of FEAU determinations performed on isolates from tear film and on the virus inoculum in secondary rabbit kidney cultures yielded a range of 4.6-7 μM, with two in vitro resistant isolates having ED50s of ≥ 1500 μM of FEAU. Fifty percent cell growth inhibition for FEAU was 3000 μM at 72 h. © 1992.
Keywords: drug efficacy; nonhuman; animal; cells, cultured; animal experiment; animal model; aciclovir; drug evaluation, preclinical; herpes virus; simplexvirus; arabinofuranosyluracil; disease models, animal; antiviral activity; feau; acyclovir; antiviral agents; 5 ethyl 2' fluorouracil arabinoside; rabbits; herpesvirus; rabbit; herpes simplex keratitis; keratitis, herpetic; cornea; antiviral; nucleoside derivative; male; priority journal; article; support, u.s. gov't, p.h.s.; ophthalmic solutions; ocular disease
Journal Title: Antiviral Research
Volume: 17
Issue: 2
ISSN: 0166-3542
Publisher: Elsevier Science, Inc.  
Date Published: 1992-02-01
Start Page: 157
End Page: 167
Language: English
DOI: 10.1016/0166-3542(92)90049-b
PUBMED: 1313221
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026501053&doi=10.1016%2f0166-3542%2892%2990049-B&partnerID=40&md5=5a2b71705b7f9f7c61dca81196b467ad
Notes: Article -- Export Date: 30 July 2019 -- Source: Scopus
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MSK Authors
  1. Kyoichi A Watanabe
    125 Watanabe
  2. Jack J. Fox
    27 Fox
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