Inhibitory effect of artemisinin-sulfadoxine-pyrimethamine combination on the development of drug-resistance in Plasmodium berghei

By increasing drug pressure during successive weekly passages of Plasmodium berghei (K173 strain) infection in mice, the retardative effects of artemisinin-sulfadoxine-pyrimethamine combination [Art+(Sul-Pyr)] on the rate of development of drug resistance in parasites were investigated. The results revealed that this drug combination markedly decreased the rate of development of resistance to the individual components. After 80 passages over 560 d, the resistant indices of Art and Sul-Pyr resistant lines were 5.7 and 118.6, respectively, while that of the Art+(Sul-Pyr) resistant line was only 3.5. In addition, the maximum tolerated dose of the Art+(Sul-Pyr) line was far less than that for each individual compound. The maximum tolerated doses for the Art and Sul-Pyr lines were 500 and 17 mg/kg, respectively, while those for Art+(Sul-Pyr) line was 229 and 0.75 mg/kg, respectively. The results suggest that the optimal combination of Art and Sul-Pyr is at a ratio of 400:1.