Comparison of β-Artemether and β-Arteether against Malaria Parasites In vitro and In vivo

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  • Division of Experimental Therapeutics, and Division of Biometrics, Walter Reed Army Institute of Research, Gorgas Memorial Laboratory, Center for Tropical Parasitic Diseases, University of Miami School of Medicine, Pharmaceutical Systems, Inc., Washington, DC, Panama

The antimalarial activity of β-artemether and β-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum. In vitro, the mean 50% inhibitory concentration (IC50) for β-artemether was 1.74 nM (range 1.34–1.81 nM), and this value for β-arteether was 1.61 nM (range 1.57–1.92 nM). They were approximately 2.5-fold more potent than artemisinin, which had a mean IC50 of 4.11 nM (range 3.36–4.60 nM). In the mouse model, the 50% curative doses (CD50) of β-artemether and β-arteether had a mean value of 55 mg/kg (32–78 mg/kg). The 50% effective curative doses (ED50) in the Aotus monkey were 7.1 mg/kg (95% confidence interval [CI] = 3.7–13.5) for β-artemether and 11.8 mg/kg (95% CI = 6.5–21.3) for β-arteether. Overall, the activities of the two drugs were comparable.