Efficacy of artemisinin and mefloquine combinations against Plasmodium falciparum. In vitro simulation of in vivo pharmacokinetics
Neither artemisinin nor mefloquine alone provided radical clearance of P. falciparum, even when maximum concentrations (10−5 m) were applied. The antiparasitic activity of artemisinin and mefloquine were significantly higher when dosed alone. Effective concentrations for different degrees of inhibition (EC 50, 90 and 99) of both artemisinin and mefloquine respectively were significantly lower when used in combination. At concentrations normally reached in vivo, this effect was clearly synergistic (P=0.016)
Our in vitro model of intermittent dosing of artemisinin and mefloquine combinations for 3 days provides significant evidence of positive interaction between the two compounds. Lower combination concentrations around the MIC‐values for the individual compounds showed synergistic effect, and high concentrations showed additive effect. This indicates that such drug combinations may provide radical clearance at concentrations lower than those required for single‐drug treatment.
Document Type: Original Article
Affiliations: 1: Division of Infectious Diseases, Karolinska Institutet, Huddinge, Sweden, 2: Division of Infectious Diseases, Karolinska Institutet, Danderyd, Sweden, 3: Institute of Specific Prophylaxis & Tropical Medicine, University of Vienna, Vienna, Austria
Publication date: 1997-05-01