Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis.
The efficacy of a new class of drugs for Pneumocystis carinii pneumonitis was demonstrated. 566C80, a hydroxynaphthoquinone, administered orally in a dose of greater than or equal to 100 mg/kg of body weight per day prophylactically prevented P. carinii pneumonitis in 90% or more of rats, while all untreated control animals developed pneumonitis. When 566C80 (100 mg/kg per day) was administered for 3 weeks after P. carinii pneumonitis was established, therapy was totally effective and all of the untreated controls had progressive P. carinii pneumonitis. A dose of 566C80 of between 25 and 50 mg/kg per day protected 50% of the rats from P. carinii pneumonitis, and a dose of between 50 and 100 mg/kg per day cured 50% of those treated for P. carinii pneumonitis. Both prophylaxis and treatment with 566C80 were at least as effective as with trimethoprim-sulfamethoxazole. Animals maintained on immunosuppression after completion of treatment remained free of P. carinii, suggesting a killing effect. Clearance of P. carinii was associated with levels of 60 micrograms or more of 566C80 per ml of plasma. This hydroxynaphthoquinone offers promise as an anti-P. carinii drug.
Hughes
W T
WT
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Gray
V L
VL
Gutteridge
W E
WE
Latter
V S
VS
Pudney
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053626:Atovaquone; D003907:Dexamethasone / Q000627:therapeutic use; D008168:Lung / Q000473:pathology; D008297:Male; D009285:Naphthoquinones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013754:Tetracyclines / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000890:Anti-Infective Agents; D009285:Naphthoquinones; D013754:Tetracyclines; D003907:Dexamethasone; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D053626:Atovaquone