TOPICAL HPMPC INHIBITS ADENOVIRUS TYPE-5 IN THE NEW-ZEALAND RABBIT OCULAR REPLICATION MODEL

Purpose. To evaluate the antiviral inhibitory activity of HPMPC agains t ocular adenoviral serotypes in vitro and to determine the therapeuti c efficacy and ocular toxicity of treatment with topical HPMPC on esta blished adenovirus type 5 (AD5) McEwen infection in the New Zealand (N Z) rabbit ocular replication model. Methods. The 50% inhibitory dose ( ID50) of HPMPC was determined for various clinical isolates of AD5 and AD8 by plaque assay in A549 cells. In vivo inhibitory effects were me asured by serial ocular titers and duration of viral shedding in the A D5-NZ rabbit ocular model. Local ocular toxicity was evaluated by exte rnal and slit lamp examination for blepharitis, conjunctivitis, kerati tis, and iritis. Results. The mean ID50 for seven isolates of AD8 was 0.47 (range, 0.02 mu g/ml to 0.82 mu g/ml), and the mean ID50 for seve n isolates of AD5 was 1.03 (range, 0.15 mu g/ml to 2.80 mu g/ml). In a series of in vivo experiments, topical administration of HPMPC for as long as 10 days (total dose, >2.8 mg) significantly reduced both AD5 ocular titers and the number of days of viral shedding compared to tha t for vehicle-treated control eyes. Local ocular toxicity was not clin ically significant at a total dose of <10 mg administered for as long as 10 days. Conclusions. HPMPC, a broad-spectrum, long-acting nucleosi de monophosphate analog, is a promising candidate for the treatment of epidemic keratoconjunctivitis infections. Further studies to ensure s afety and efficacy in humans are warranted.