Activity of lipid-soluble inhibitors of dihydrofolate reductase against Pneumocystis carinii in culture and in a rat model of infection.
Trimetrexate and BW301U (piritrexim isethionate), lipid-soluble inhibitors of dihydrofolate reductase, are potent inhibitors of the growth of Pneumocystis carinii in culture with WI-38 cells. Inhibition was observed with 0.1 microgram of trimetrexate or BW301U per ml. Trimethoprim is ineffective at 100 micrograms/ml in this culture system. Both trimetrexate and BW301U were effective as prophylactic agents against P. carinii pneumonia in rats; trimetrexate at 7.5 mg/kg protected 9 of 10 rats, and BW301U at 5 mg/kg protected 4 of 10.
D000818:Animals; D002478:Cells, Cultured; D005493:Folic Acid Antagonists; D006801:Humans; D011010:Pneumocystis / Q000187:drug effects* / Q000254:growth & development; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D016597:Trimetrexate
D005493:Folic Acid Antagonists; D011743:Pyrimidines; D011799:Quinazolines; D012313:RNA; C024530:piritrexim; D016597:Trimetrexate