Activities of pefloxacin and ciprofloxacin against experimental malaria in mice

We investigated the in vivo antimalarial activities of pefloxacin and ciprofloxacin in Swiss albino mice infected intravenously with 5 x 10(6) Plasmodium yoelii N67 parasites 1 h before treatment. Groups of 20 mice received a subcutaneous injection of 40, 80, or 160 mg of ciprofloxacin or pefloxacin per kg of body weight every 8 h for 3 days. Parasitologic activity was assessed on day 4, and survival was assessed on day 21. Control mice had a fulminant course with a parasitemia of 61.3% +/- 12.1% on day 4, and 90% of the mice were dead on day 21. The lower dosages of pefloxacin and ciprofloxacin (40 and 80 mg/kg) were not efficient. With 160 mg/kg, ciprofloxacin achieved an 85.8% reduction in parasitemia and 17 of 20 mice survived. Pefloxacin achieved a 92.8% reduction in parasitemia, and all mice survived. All treated, noninfected control mice survived. With ciprofloxacin, the antimalarial activity was similar with injections of 240 mg/kg every 12 h but was strongly diminished with injections of 160 mg/kg every 12 h. With pefloxacin, similar activities were observed with injections of 160 mg/kg every 8 h or injections of 160 or 240 mg/kg every 12 h. With both drugs, this activity was highly reduced when the treatment was delayed by 24 h. This underlines the need to provide treatment within the first hours after infection to achieve an optimal effect in this rapidly lethal experimental model of malaria. Pefloxacin and, to a lesser extent, ciprofloxacin are potent antimalarial drugs which might prove useful in the treatment of less rapidly aggressive human malaria.

[1]  P. Sarma Norfloxacin: a new drug in the treatment of falciparum malaria. , 1989, Annals of internal medicine.

[2]  A. Sartorelli,et al.  Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro , 1988, Antimicrobial Agents and Chemotherapy.

[3]  J. Phillipson,et al.  QUINOLONES AND MULTIRESISTANT PLASMODIUM FALCIPARUM , 1988, The Lancet.

[4]  S. Krishna,et al.  CIPROFLOXACIN AND MALARIA , 1988, The Lancet.

[5]  P. Davey,et al.  The inoculum effect with gram-negative bacteria in vitro and in vivo. , 1987, The Journal of antimicrobial chemotherapy.

[6]  G. Riou,et al.  Purification and characterization of Plasmodium berghei DNA topoisomerases I and II: drug action, inhibition of decatenation and relaxation, and stimulation of DNA cleavage. , 1986, Biochemistry.

[7]  D. Hooper,et al.  The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans , 1985, Antimicrobial Agents and Chemotherapy.

[8]  D. Hooper,et al.  The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro , 1985, Antimicrobial Agents and Chemotherapy.

[9]  G. Drusano,et al.  Multiple-dose pharmacokinetics of ciprofloxacin administered intravenously to normal volunteers , 1985, Antimicrobial Agents and Chemotherapy.

[10]  J. Crane,et al.  Uptake of ciprofloxacin by human neutrophils. , 1985, The Journal of antimicrobial chemotherapy.

[11]  J. Jensen,et al.  Oxygen- and time-dependent effects of antibiotics and selected mitochondrial inhibitors on Plasmodium falciparum in culture , 1985, Antimicrobial Agents and Chemotherapy.

[12]  R. Wise,et al.  Pharmacokinetics of intravenously administered ciprofloxacin , 1984, Antimicrobial Agents and Chemotherapy.

[13]  F. Roquet,et al.  Absorption, distribution, metabolic fate, and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys, and humans , 1984, Antimicrobial Agents and Chemotherapy.

[14]  F. Castora,et al.  The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria. , 1983, Biochimica et biophysica acta.

[15]  W. Peters,et al.  The chemotherapy of rodent malaria, XXIII Causal prophylaxis, part II: Practical experience with Plasmodium yoelii nigeriensis in drug screening. , 1975, Annals of tropical medicine and parasitology.