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

Abstract

The antimalarial activity of beta-artemether and beta-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 beta-artemether was 1.74 nM (range 1.34-1.81 nM), and this value for beta-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 beta-artemether and beta-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 beta-artemether and 11.8 mg/kg (95% CI = 6.5-21.3) for beta-arteether. Overall, the activities of the two drugs were comparable.