Azithromycin: antimalarial profile against blood- and sporozoite-induced infections in mice and monkeys.
The spectrum of antimalarial activity of the new macrolide antibiotic azithromycin was evaluated against blood- and sporozoite-induced infections with a chloroquine-resistant strain of Plasmodium yoelii nigeriensis (N-67) in Swiss mice and with simian parasite Plasmodium cynomolgi B in rhesus monkeys. Against experimental rodent malaria, a 70 mg/kg/day dose showed curative blood-schizontocidal activity in a four-dose regimen administered orally from day 0 to day 3 or from day 2 to day 5 to mice harboring established infection. The curative response was also obtained with a 40 mg/kg/day dose administered in an extended seven-dose (days 0-6) regimen. Azithromycin was also effective in the causal prophylactic test, since a 50 mg/kg dose from day -1 to day +2 protected mice against P. y. nigeriensis (N-67) sporozoite challenge. In comparison, erythromycin did not show either of the above activities up to a 405 mg/kg/day dose in identical regimens. Comparison of the ED(90) values showed that azithromycin was 31-fold more effective than erythromycin as a blood schizontocide. In the simian model, trophozoite-induced infections of P. cynomolgi B were cured with 25 mg/kg/day azithromycin administered for 7 days. In the causal prophylactic test, the prepatent period was significantly extended in monkeys challenged with P. cynomolgi B sporozoites, presumably because of the growth inhibition of preerythrocytic schizonts in hepatocytes. Azithromycin did not exhibit any hypnozoitocidal (dormant exoerythrocytic stages) activity at 25 mg/kg/day in a seven-dose regimen.
Puri
S K
SK
Division of Microbiology, Central Drug Research Institute, Lucknow, 226001, India. root@cscdri.ren.nic.in
Singh
N
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use; D004917:Erythromycin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D016789:Plasmodium cynomolgi / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects*; D011319:Primaquine / Q000494:pharmacology / Q000627:therapeutic use; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000962:Antimalarials; D004917:Erythromycin; D017963:Azithromycin; D002738:Chloroquine; D011319:Primaquine; D004318:Doxycycline; D011739:Pyrimethamine