TREATMENT OF HISTOPLASMOSIS WITH MK-991 (L-743,872)

BALB/c nu/+ immunocompetent and athymic (nu/nu) mice were infected int ravenously with yeast cells of Histoplasma capsulatum. Mice were eithe r given water (controls) intraperitoneally (i.p.) or given MK-991 i.p. once daily or twice daily. Protection was measured as prolonged survi val or reduction in tissue counts, MK-991 was protective in immunocomp etent mice, prolonging survival and reducing counts in spleen and live rs at a dose as low as 0.05 mg/kg of body weight/day. MK-991 was modes tly effective in athymic mice at a higher dose, 5 mg/kg/day. These stu dies suggest that MK-991 may be appropriate for clinical development i n histoplasmosis.