Histopathologic effects of cidofovir on cartilage

To evaluate the effects of subcutaneously injected cidofovir on cartilage in a rabbit model.

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.

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.

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.

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.

B-2.