Volume 39, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Trimetrexate is a lipid-soluble antifolate that has been shown in vitro to be a much more potent inhibitor of dihydrofolate reductase than the conventionally used inhibitor trimethoprim. To evaluate the in vivo efficacy of trimetrexate, steroid-treated rats which spontaneously develop pneumonia were used. Rats treated with trimetrexate (25 mg/kg/d) plus sulfamethoxazole (250 mg/kg/d) orally responded at least as well as rats treated with trimethoprim (50 mg/kg/d) plus sulfamethoxazole. Trimetrexate alone administered orally was ineffective in treating infection, but subcutaneous (sc) trimetrexate (7 mg/kg/d) significantly decreased the intensity of infection compared to controls. Trimetrexate is a potent antifolate that may provide an effective alternative to pentamidine and trimethoprim-sulfamethoxazole for treatment of pneumonia in humans.


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