1921
Volume 54, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

is a major cause of focal encephalitis in patients with acquired immunodeficiency syndrome. Epiroprim, an inhibitor of dihydrofolate reductase, was evaluated in vitro and in a mouse model of acute infection for activity against . The 50% inhibitory concentration (IC) of epiroprim for dihydrofolate reductase was 0.9 µM, similar to that of pyrimethamine, but epiroprim was 650-fold more selective than pyrimethamine for compared with human dihydrofolate reductase. While intraperitoneally administered epiroprim (300 mg/kg/day for 14 days) alone was ineffective in mice acutely infected with the RH strain of , 100% survival was seen when it was combined with orally administered sulfadiazine (375 mg/kg/day), which alone was also ineffective. Increases in survival were seen in combination with doses of sulfadiazine as low as 0.375 mg/kg/day. Orally administered epiroprim combined with dapsone also prolonged survival. Thus, epiroprim is an active and potentially less toxic alternative to pyrimethamine for the treatment of toxoplasmosis.

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