Synergism between monodesbutyl-benflumetol and artemisinin in Plasmodium falciparum in vitro

Abstract

The sensitivity to artemisinin, monodesbutyl-benflumetol (DBB) and a 1:1 m/m combination of the two compounds was successfully investigated on 34 fresh isolates of Plasmodium falciparum. On a molar basis the combination was most active, followed by DBB and artemisinin. The geometric mean concentrations effecting full inhibition (GMCOC) were 49.25 nM for the combination, 279.12 nM for DBB, and 494.05 for artemisinin. The difference between the efficacy of the combination and that of its components was highly significant. Interaction between artemisinin and DBB showed moderate synergism at the EC50and strong synergism at EC90and EC99. The individual parasite isolates showed a significant inverse correlation between the ECs and the degree of synergism. Positive specific pharmacodynamic interaction was therefore most marked in isolates with reduced sensitivity against artemisinin and DBB. © 2008 Springer-Verlag.