Local and systemic effects of intralaryngeal injection of cidofovir in a canine model.
OBJECTIVE
The safety of intralaryngeal injection of cidofovir remains a concern. Our goal was to evaluate local and systemic effects of intralaryngeal injection of cidofovir.


METHODS
Animal study using a canine model.


METHODS
Two groups of three young beagle dogs (6 vocal folds in each group) were used. Subepithelial vocal fold injections were performed in each group biweekly for 6 months with 0, 2.5, 5, 10, 20, and 37.5 mg cidofovir in a 0.5 mL volume. Direct laryngoscopy was performed at each injection interval. Complete blood cell count and renal parameters were measured at baseline and monthly thereafter. Histopathologic examination of the vocal folds was performed after the 6-month injection period in one group of animals and after an additional 6-month observation period in the second group.


RESULTS
Endomysial edema with muscle fiber separation and dose-dependent atrophy and scarring of the vocal folds was present. Onset of atrophy and scarring was observed after 3, 7, and 11 injections in the vocal folds injected with 37.5, 20, and 10 mg cidofovir, respectively. After the 6-month observation period, recovery of histologic abnormalities was complete in the low-dose (0, 2.5 mg) vocal folds, near complete in the intermediate-dose (5, 10 mg) vocal folds, and no apparent recovery was seen in the high-dose (20, 37.5 mg) vocal folds. Leukocyte count and renal parameters remained unchanged at up to 4.26 mg/kg body weight of systemic dose of cidofovir.


CONCLUSIONS
Intralaryngeal cidofovir leads to dose-dependent scarification of the vocal folds that appears irreversible at higher doses. Lower concentrations of this drug should be used in intralesional intralaryngeal use.
Chhetri
Dinesh K
DK
Division of Head and Nack Surgery, University of California Los Angeles School of Medicine, 90095, USA. dchhetri@ucla.edu
Jahan-Parwar
Babak
B
Hart
Stephen D
SD
Bhuta
Sunita M
SM
Berke
Gerald S
GS
Shapiro
Nina L
NL
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D001806:Blood Urea Nitrogen; D000077404:Cidofovir; D003404:Creatinine / Q000378:metabolism; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular; D007668:Kidney / Q000187:drug effects; D007819:Laryngeal Edema / Q000139:chemically induced / Q000473:pathology; D007821:Laryngeal Muscles; D007830:Larynx / Q000187:drug effects* / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects; D009336:Necrosis; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014827:Vocal Cords / Q000187:drug effects / Q000473:pathology
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D003404:Creatinine; D000077404:Cidofovir