Efficacy of epiroprim (Ro11-8958), a new dihydrofolate reductase inhibitor, in the treatment of acute Toxoplasma infection in mice

Anthony Martinez, Carmen J. Allegra, Joseph A. Kovacs

Research output: Contribution to journalArticle

Abstract

Toxoplasma gondii 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 T. gondii. The 50% inhibitory concentration (IC50) of epiroprim for T. gondii dihydrofolate reductase was 0.9 μM, similar to that of pyrimethamine, but epiroprim was 650-fold more selective than pyrimethamine for T. gondii 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 T. gondii, 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.

Original languageEnglish (US)
Pages (from-to)249-252
Number of pages4
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume54
Issue number3
DOIs
StatePublished - Mar 1996

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ASJC Scopus subject areas

  • Parasitology
  • Virology
  • Infectious Diseases

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