Synergism between monodesbutyl-benflumetol and artemisinin in Plasmodium falciparum in vitro.
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 EC(50) and strong synergism at EC(90) and EC(99). 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.
Müller
Gernot
G
Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria.
Wernsdorfer
Gunther
G
Sirichaisinthop
Jeeraphat
J
Starzengruber
Peter
P
Congpuong
Kanungnit
K
Wernsdorfer
Walther H
WH
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D005449:Fluorenes / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013785:Thailand
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; C435716:desbutylbenflumetol; C031327:artemisinin