EFFICACY OF ORAL SAPERCONAZOLE IN SYSTEMIC MURINE ASPERGILLOSIS

Saperconazole is a fluorinated bis-triazole. Groups of ten 5-week-old female CD-1 mice were infected intravenously with 5.5 x 10(7) Aspergil lus conidia. Saperconazole, dissolved in hydroxypropyl-beta-cyclodextr in (HPBC), was given orally twice a day for 11 days, beginning 1 day p ost-infection, at 50, 100 or 200 mg kg(-1) day(-1). At day 18 post-inf ection, survivors were killed and residual infection quantified in the kidneys. With Aspergillus fumigatus isolate 10AF, 70% given no therap y, 100% given daily oral HPBC and 40% given intraperitoneal amphoteric in B at 3.3 mg kg(-1) three times a week for 2 weeks died, whereas all mice given saperconazole survived. Each saperconazole regimen prolong ed survival compared to untreated or HPBC-treated mice (P < 0.01). Sap erconazole at 200 mg kg(-1) day(-1) reduced colony forming units of as pergillus in kidneys more than 1000-fold compared to untreated or HPBC treated mice (P < 0.001) and saperconazole regimens were superior to amphotericin B therapy (P < 0.01). In another study of the same design with A. fumigatus isolate 15AF, 90% of untreated and 20% of mice trea ted with saperconazole at 50 mg kg(-1) day(-1) died; all others surviv ed. Any saperconazole regimen prolonged survival (P < 0.001). Residual infection was also significantly reduced by all saperconazole regimen s (P < 0.01). With Aspergillus terreus isolate 4AT, 80% of untreated m ice, 50% of mice treated with saperconazole at 50 mgkg(-1) day(-1) and 10% of mice treated at 200 mg kg(-)1 day(-1) died. Any saperconazole regimen prolonged survival (P < 0.05). Saperconazole at 100 and 200 mg kg(-1) day(-1) also reduced residual infection (P < 0.001). No adverse effects were noted in any study. Thus, saperconazole was efficacious in vivo against different Aspergillus isolates.