Relative potency of 10 drugs with anti-Pneumocystis carinii activity in an animal model.
Several drugs have been shown to have anti-Pneumocystis carinii activity in clinical trials. Because of the large number of patients required, no more than 3 drugs can be compared for efficacy in human studies. However, the experimental animal model for P. carinii pneumonitis is remarkably similar to the human disease and was used to compare 10 drugs for the relative potency against this infection. All drugs were compared at doses known to prevent the pneumonitis in > 80% of animals and at one-tenth of this dose. Drugs effective at the lowest dose were further tested at one-hundredth the original doses, and drugs ineffective were retested at 10 and 100 times the original dose. Trimethoprim-sulfamethoxazole was the most effective drug, with azithromycin-sulfamethoxazole and clarithromycin-sulfamethoxazole next most effective. Intravenous pentamidine and clindamycin-primaquine were the least effective. Atovaquone, sulfadoxine-pyrimethamine, erythromycin-sulfisoxazole, PS-15, and dapsone-trimethoprim had intermediate activity.
Hughes
W T
WT
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Killmar
J T
JT
Oz
H S
HS
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D053626:Atovaquone; D017963:Azithromycin / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D002981:Clindamycin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003622:Dapsone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D006801:Humans; D009285:Naphthoquinones / Q000627:therapeutic use; D010419:Pentamidine / Q000627:therapeutic use; D016720:Pneumocystis Infections / Q000188:drug therapy*; D002727:Proguanil / Q000031:analogs & derivatives / Q000627:therapeutic use; D011739:Pyrimethamine / Q000627:therapeutic use; D051381:Rats; D013413:Sulfadoxine / Q000627:therapeutic use; D013420:Sulfamethoxazole / Q000627:therapeutic use; D014295:Trimethoprim / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000890:Anti-Infective Agents; D009285:Naphthoquinones; C082651:PS 15; D002981:Clindamycin; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D017963:Azithromycin; D013413:Sulfadoxine; D003622:Dapsone; D014295:Trimethoprim; D017291:Clarithromycin; D013420:Sulfamethoxazole; D002727:Proguanil; D053626:Atovaquone; D011739:Pyrimethamine