Effects of diclofenac or ketorolac on the inhibitory activity of cidofovir in the Ad5/NZW rabbit model.
OBJECTIVE
The goal of this study was to determine the effects of concurrent therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) on the antiviral activity of cidofovir on adenovirus replication and the formation of subepithelial infiltrates in the Ad5/New Zealand White rabbit ocular model.


METHODS
According to two protocols, 20 rabbits were inoculated in both eyes with Ad5 topically to study adenovirus replication, and 20 rabbits were inoculated in both eyes topically and intrastromally to study the formation of subepithelial infiltrates. Animals were randomized to four masked treatment groups: group I, 0.5% cidofovir + artificial tears; group II, 0.5% cidofovir + 0.5% ketorolac tromethamine; group III, 0.5% cidofovir + 0.1% diclofenac sodium; and group IV, control + artificial tears. Cidofovir and control were administered to both eyes twice daily for 7 days, and artificial tears, ketorolac, and diclofenac four times daily for 14 days. Eyes were cultured on days 0, 1, 3, 4, 5, 7, 9, 11, and 14.


RESULTS
Compared with the control group, all cidofovir-treated groups demonstrated significant antiviral effects on adenovirus replication. There were no differences in adenovirus replication among the cidofovir-treated groups (I, II, and III), nor were there any differences among all groups (I-IV) in the formation of subepithelial infiltrates.


CONCLUSIONS
Concurrent treatment of ketorolac or diclofenac with cidofovir did not diminish its antiviral inhibitory activity on adenovirus replication, nor did it prevent the formation of subepithelial infiltrates in the rabbit model.
Romanowski
E G
EG
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Gordon
Y J
YJ
D000258:Adenovirus Infections, Human / Q000188:drug therapy* / Q000821:virology; D000260:Adenoviruses, Human / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077404:Cidofovir; D003319:Corneal Stroma / Q000187:drug effects / Q000821:virology; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000821:virology; D005260:Female; D006801:Humans; D007634:Keratitis / Q000188:drug therapy* / Q000821:virology; D020911:Ketorolac Tromethamine / Q000009:adverse effects / Q000627:therapeutic use; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000627:therapeutic use; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D004008:Diclofenac; D020911:Ketorolac Tromethamine; D003596:Cytosine; D000077404:Cidofovir