• Antiviral therapy · Jan 2014

    Safety of cidofovir by intratympanic delivery technique.

    • Jonette A Ward, Douglas R Sidell, Michel Nassar, Alisa L Reece, and Daniel I Choo.
    • Department of Otolaryngology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. jonetteamy.ward@cchmc.org.
    • Antivir. Ther. (Lond.). 2014 Jan 1; 19 (1): 97-105.

    BackgroundCongenital cytomegalovirus (CMV) infection is one of the most common infectious causes of congenital sensorineural hearing loss. To date, a safe and effective therapy for CMV-induced hearing loss does not exist. We hypothesize that the antiviral cidofovir (CDV) can be delivered to the inner ear via intratympanic (IT) injections to safely and effectively mitigate CMV-induced hearing loss.MethodsTo evaluate the safety of CDV IT injections, weanling guinea pigs with normal hearing were injected intratympanically with 3 mg or 5 mg concentrations of CDV and compared to control animals injected with sterile saline. A separate group of weanling guinea pigs were inoculated with CMV and a subset of this group was treated with CDV following inoculation.ResultsThe 3 mg/ml and 5 mg/ml CDV concentrations resulted in hearing loss following IT injection into uninfected animals. No signs of inflammation or toxicity were noted on histologic analysis and there was no evidence of systemic toxicity in serology. Hearing loss induced as a result of guinea pig CMV infection recovered by day 21 in animals treated with IT injections of 5 mg/ml CDV.ConclusionsWe provide promising evidence demonstrating both the efficacy and safety of IT CDV in the guinea pig animal model. This research further establishes a sound framework upon which ongoing investigations into drug delivery mechanisms for CMV-induced hearing loss will be based.

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