Efficacy of azithromycin as a causal prophylactic agent against murine malaria.
The efficacy of the newly marketed azalide azithromycin was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria. Drug was administered once; Plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined. For parenterally administered drug, 160 mg of azithromycin or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective. Orally administered azithromycin was somewhat less effective than parenterally administered drug, consistent with the 37% clinical oral bioavailability of this agent. For orally administered azithromycin, 160 mg/kg was 100% effective and 40 mg/kg was 40% effective. The efficacy of azithromycin in comparison with that of doxycycline and the known prolonged levels of azithromycin in the livers of humans suggest that azithromycin has potential as a clinical causal prophylactic agent for malaria.
Andersen
S L
SL
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Ager
A L
AL
McGreevy
P
P
Schuster
B G
BG
Ellis
W
W
Berman
J
J
D000818:Animals; D017963:Azithromycin / Q000627:therapeutic use*; D004318:Doxycycline / Q000627:therapeutic use; D005260:Female; D008288:Malaria / Q000517:prevention & control*; D051379:Mice; D010967:Plasmodium yoelii
D017963:Azithromycin; D004318:Doxycycline