Efficacy of trimetrexate, a potent lipid-soluble antifolate, in the treatment of rodent Pneumocystis carinii pneumonia.

Abstract

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.

• Authors: J A Kovacs, C J Allegra, S Kennedy, J C Swan, J Drake, J E Parrillo, B Chabner, H Masur
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 39 Issue 5 Pg. 491-6 (Nov 1988) ISSN: 0002-9637 [Print] United States
• PMID: 2973755 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Folic Acid Antagonists
• Quinazolines
• Trimethoprim
• Sulfamethoxazole
• Trimetrexate

Topics

• Administration, Oral
• Animals
• Drug Therapy, Combination
• Folic Acid Antagonists (administration & dosage, therapeutic use)
• Injections, Subcutaneous
• Male
• Pneumonia, Pneumocystis (drug therapy)
• Quinazolines (administration & dosage, therapeutic use)
• Rats
• Rats, Inbred Strains
• Sulfamethoxazole (therapeutic use)
• Trimethoprim (therapeutic use)
• Trimetrexate