| Title | The In Vitro and In Vivo Evaluation of ddC as a Topical Antiviral for Ocular Adenovirus Infections. | | Author(s) | Romanowski EG, Yates KA, Gordon YJ | | Institution | Charles T. Campbell Laboratory, Department of Ophthalmology, University of Pittsburgh, The Eye & Ear Institute, Pittsburgh, Pennsylvania, 15213, United States. | | Source | Invest Ophthalmol Vis Sci 2009 Jun 10. | | Abstract | Purpose: To evaluate the antiviral activity of 2', 3'-dideoxycytidine (ddC) in vitro against a panel of ocular adenovirus serotypes and in vivo in the ocular Ad5/NZW rabbit replication model.
Methods: In vitro, the 50% inhibitory concentrations (IC50) of ddC and cidofovir were determined using standard plaque reduction assays. In vivo, 40 rabbits were topically inoculated in both eyes with Ad5 following corneal scarification. On day 1, the rabbits were equally divided into 4 topical treatment groups: 1) 3% ddC; 2) 2% ddC; 3) 0.5% cidofovir; and 4) saline. ddC and saline eyes were treated 4 times daily for 7 days, while cidofovir treated eyes were treated twice daily for 7 days. Eyes were cultured for virus multiple times over two weeks.
Results: The in vitro IC50s for ddC ranged from 0.18 to 1.85 microg/ml while those for cidofovir ranged from 0.018 microg/ml to 5.47 microg/ml. ddC was more potent than cidofovir for 7 of 9 serotypes. In vivo, 3% ddC, 2% ddC, and 0.5% cidofovir significantly reduced the number of Ad5 Positive Cultures per Total (Days 1-14), Mean Ad5 Ocular Titer (Days 1-5), and Duration of Shedding (among other outcome measures) compared with the saline control. 3% and 2% ddC were significantly more efficacious than 0.5% cidofovir in the parameters listed above.
Conclusions: ddC demonstrated potent anti-adenoviral activity in vitro and in vivo. Systemic safety studies following topical ocular administration are required to evaluate ddC as a topical antiviral treatment for adenoviral ocular infections in its target population. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19516011 |
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