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


METHODS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.


METHODS
B-2.
Spiegel
Jeffrey H
JH
Department of Otolaryngology-Head and Neck Surgery, Boston University School of Medicine, Boston Medical Center, MA 02118, USA. jeffrey.spiegel@bmc.org
Andrus
Jennifer G
JG
Stefanato
Catherine M
CM
Heeren
Timothy
T
D000818:Animals; D001707:Biopsy, Needle; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology*; D000077404:Cidofovir; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004431:Ear, External / Q000187:drug effects / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D023421:Models, Animal; D063065:Organophosphonates / Q000009:adverse effects / Q000494:pharmacology*; D011817:Rabbits; D012680:Sensitivity and Specificity
D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir