Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases

Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe o ral therapy would be ideal. We examined the efficacy of SCH 56592, an inves tigational triazole antifungal agent, against cutaneous infection with Leis hmania amazonensis and visceral infection with Leishmania donovani in BALB/ c mice. Mice were infected in the ear pinna and tail with L, amazonensis pr omastigotes and were treated with oral SCI-I 56592 or intraperitoneal ampho tericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highl y efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day, The means of t ail lesion sizes were 0.32 +/- 0.12, 0.11 +/- 0.06, 0.17 +/- 0.07, and 0.19 +/- 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphoteric in B recipients, respectively (P = 0.00113, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/ day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. Th ese studies indicate very good activity of SCH 56592 against cutaneous leis hmaniasis due to L, amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c m ice.