Efficacy of trimetrexate, a potent lipid-soluble antifolate, in the treatment of rodent Pneumocystis carinii pneumonia.
Trimetrexate is a lipid-soluble antifolate that has been shown in vitro to be a much more potent inhibitor of Pneumocystis carinii dihydrofolate reductase than the conventionally used inhibitor trimethoprim. To evaluate the in vivo efficacy of trimetrexate, steroid-treated rats which spontaneously develop P. carinii 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 P. carinii 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 P. carinii pneumonia in humans.
Kovacs
J A
JA
Critical Care Medicine Department, National Cancer Institute, Bethesda, Maryland 20892.
Allegra
C J
CJ
Kennedy
S
S
Swan
J C
JC
Drake
J
J
Parrillo
J E
JE
Chabner
B
B
Masur
H
H
D000284:Administration, Oral; D000818:Animals; D004359:Drug Therapy, Combination; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013420:Sulfamethoxazole / Q000627:therapeutic use; D014295:Trimethoprim / Q000627:therapeutic use; D016597:Trimetrexate
D005493:Folic Acid Antagonists; D011799:Quinazolines; D014295:Trimethoprim; D013420:Sulfamethoxazole; D016597:Trimetrexate