Evaluation of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil in a rabbit model of herpetic keratitis.
The nucleoside analog 1-(2'-deoxy-2'-fluoro-beta-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 microM, with two in vitro resistant isolates having ED50S of greater than or equal to 1500 microM of FEAU. Fifty percent cell growth inhibition for FEAU was 3000 microM at 72 h.
Trousdale
M D
MD
Doheny Eye Institute, Los Angeles, CA 90033.
Law
J L
JL
Yarber
F A
FA
Watanabe
K A
KA
Fox
J J
JJ
D000212:Acyclovir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D003315:Cornea / Q000382:microbiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification
D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D001086:Arabinofuranosyluracil; C052341:1-(2-deoxy-2-fluoroarabinofuranosyl)-5-ethyluracil; D000212:Acyclovir