Activity of ICI 195,739--a novel, orally active bistriazole--in rodent models of fungal and protozoal infections.
ICI 195,739 shows superior potency to other azoles in eliminating vaginal candidosis or dermatophyte infections in animal models of infection by both oral dosing and topical application; effective doses are in the range of 0.5-5.0 mg/kg/day or 0.01-0.30% in a topical formulation. ICI 195,739 is likewise effective in models of systemic fungal infection; 1, 10, 25 mg/kg/day will protect animals given a lethal inoculum of C. albicans, C. neoformans, or A. fumigatus, respectively, as long as dosing is continued, showing activity in this respect superior to that of other azoles tested. ICI 195,739 will suppress infections in mice with T. cruzi and prevent mortality with five daily doses of 1 mg/kg; cure rather than suppression of patent infections has been achieved with 35 daily doses of 10 mg/kg.
Ryley
J F
JF
ICI Pharmaceuticals Division, Mereside, Alderley Park, Macclesfield, Cheshire, England.
McGregor
S
S
Wilson
R G
RG
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D014005:Tinea / Q000188:drug therapy*; D014230:Triazoles / Q000627:therapeutic use*; D014352:Trypanosomiasis / Q000188:drug therapy*
D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D014230:Triazoles; C058219:ICI 195739