TABLE 1

In vivo efficacy of KAF156 in a P. berghei rodent malaria modela

Dose(s) (mg/kg)CompoundbMean ± SDCure (%)d
Activity (%)Mouse survival (days)c
1 × 30Chloroquine*99.9 ± 0.079.6 ± 0.80
Mefloquine*99.6 ± 0.521.8 ± 2.10
Artesunate*92.4 ± 2.99.0 ± 1.20
KAF156†99.9 ± 0.00616.7 ± 2.80
1 × 100Chloroquine*99.912.70
Artesunate*99.9 ± 0.088.8 ± 0.80
KAF156†99.9 ± 0.00823.4 ± 4.310
3 × 30Chloroquine‡99.9 ± 0.0214.0 ± 0.00
Mefloquine‡98.6 ± 0.318.8 ± 1.30
Artesunate‡99.0 ± 0.311.8 ± 3.30
3 × 50KAF156†>99.9929.4 ± 0.840
4 × 100KAF156†>99.9929.8 ± 0.690
  • a A comparison of single- and multiple-dose efficacies with standard antimalarials or KAF156 was performed. For single-dose efficacy, the mice were dosed 24 h after infection. The percent parasitemia was measured 72 h after infection, and mouse survival was monitored. For multiple-dose efficacy, the mice were dosed daily for 3 days (24, 48, and 72 h after infection) or 4 days (6, 24, 48, and 72 h after infection [see column 1]) at the indicated doses. The percent parasitemia was measured 96 h after infection, and mouse survival was monitored. GFP-ANKA was used in the reference study with chloroquine, mefloquine, and artesunate, and parasitemia was determined by fluorescence-activated cell sorting analysis. No significant differences were observed with GFP-ANKA and ANKA strains for these compounds. Data are means calculated from two independent experiments, with n = 5 mice for each experiment.

  • b *, Ethanol-Tween 80-water (3/7/90); †, 5% Solutol HS15; ‡, 10% ethanol, 30% PEG400, 60% Vit E TPGS.

  • c The survival of control animals was 6 to 7 days.

  • d Cure, no parasites present at day 30.