title: Efficacy of voriconazole in experimental rat paracoccidioidomycosis.
abstract: BACKGROUND
  Amphotericin B, azole or sulfamide drugs are used for treatment of patients with paracoccidioidomycosis. Among the azole drugs, voriconazole was active in vitro against Paracoccidioides brasiliensis and showed efficacy in the treatment of patients infected with this fungus.In the present study the antifungal activity of voriconazole and of other drugs was compared in a rat model of paracoccidioidomycosis.
  
  
  METHODS
  Wistar rats were inoculated intravenously with the BOAS strain of P. brasiliensis and antifungal drugs were administered to the animals by gavage at the following doses (mg/kg weight/day): voriconazole (5 to 20), ketoconazole (12 to 15), fluconazole (6), itraconazole (4), and sulfamethoxazole-trimethoprim (120 to 150). The antifungal activity of the drugs was assessed by determining the P. brasiliensis colony forming units in the lungs and spleen of the animals at the end of treatment and by a survival study.
  
  
  RESULTS
  Voriconazole reduced the total tissue fungal burden of P. brasiliensis, particularly at doses of ≥ 10 mg/kg weight/day but its antifungal activity was less intense than that of fluconazole, itraconazole and sulfamethoxazole-trimethoprim. The mean survival of animals treated with the last three drugs, 29.1 ± 10.7, 26.1 ± 10.1 and 28.4 ± 9.6 days, respectively, was higher than that achieved with voriconazole 10mg/kg weight/day (18.5 ± 8.3 days) and that observed in untreated animals (15.7 ± 3.6 days).
  
  
  CONCLUSIONS
  At doses similar to those used for clinical treatment, voriconazole showed lower antifungal activity in experimental rat paracoccidioidomycosis than that obtained with itraconazole and sulfamethoxazole-trimethoprim.
authors.affiliation: Programa de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: Daniela Silva
authors.initials: DS
authors.lastname: Granzoto
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Vitali
authors.forename: Roberto
authors.initials: R
authors.lastname: Martinez
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D010229:Paracoccidioidomycosis / Q000188:drug therapy*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole