Intranasal treatment of cowpox virus respiratory infections in mice with cidofovir

Orthopoxvirus infections in mice have been effectively treated with cidofov ir, a clinically approved drug given by intravenous infusion to treat cytom egalovirus infections. In a bioterrorist scenario it would be technically d ifficult to give this drug to a large number of exposed individuals. New tr eatment approaches are being sought, which include giving cidofovir by alte rnative routes or designing oral prodrugs of cidofovir. In this report, int ranasal cidofovir was investigated as a treatment of pulmonary cowpox virus infections in BALB/c mice. Ninety to 100% of animals given a single intran asal drug treatment (10, 20 or 40 mg/kg) 24 h after virus challenge survive d the infection, whereas all placebo-treated mice died. Doses of 2.5 and 5 mg/kg resulted in 60 and 80% survival, respectively. Single treatments of 7 0 and 40 mg/kg could be given up to 3 days after virus inoculation and stil l be 80-90% protective. A single 40 mg/kg treatment of infected mice given 1 or 2 days after infection also resulted in statistically significant decr eases in virus titer in lungs and nose/sinus compared to the placebo group. Drug efficacy was found to be contingent upon treatment volume. A 10 mg/kg intranasal dose given 24 h after virus challenge was 100 and 50% effective in volumes of 40 and 20 mu l, respectively. The same dose in 5 and 10 mu l volumes caused no decrease in mortality. The results of these studies esta blish the utility of cidofovir treatment of poxvirus infections in mice by intranasal route. The data suggest the possibility that aerosol delivery of cidofovir to human lungs may be a viable alternative to intravenous dosing . (C) 2000 Elsevier Science B.V. All rights reserved.