Comparison of β-artemether and β-arteether against malaria parasites in vitro and in vivo

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.