Histopathologic effects of cidofovir on cartilage.

OBJECTIVE: To evaluate the effects of subcutaneously injected cidofovir on cartilage in a rabbit model. STUDY DESIGN: Prospective study. The ears of 6 New Zealand White rabbits received perichondrial injection at 2 sites each of 0.1 mL of cidofovir in concentrations of 75 mg/mL, 25 mg/mL, 5 mg/mL, and 0 mg/mL. Animals were monitored for 6 weeks, and then injection sites excised and evaluated for histopathologic changes in epithelium, perichondrium, and cartilage. RESULTS: A positive dose-response relationship existed for gross skin changes; however, there was no dose-response relationship for severity of change in the epithelium. There was a temporal component to gross changes, demonstrating peak incidence and severity between 2 and 3 weeks after injection, with resolution of most changes within the 6-week study period. There was an increased likelihood of cartilage change when injecting cidofovir, but no clear relationship with injected dose. CONCLUSION: We report the first evaluation of the local effects of cidofovir injection on cartilage. The results of this study using a rabbit model suggest that delayed skin changes or histopathologic change in the cartilage may be expected in approximately one third of sites injected. Although there was a statistical likelihood for increased local change after cidofovir injection, there was no correlation of severity with injected dose. SIGNIFICANCE: Higher doses of cidofovir than commonly are used in the treatment of recurrent respiratory papillomatosis may be safe to use, although the effects of repeat application and long-term complications are not yet evident. EBM RATING: B-2.