Drug interaction studies of H2-receptor antagonists with mefloquine, pyrimethamine and sulfadoxine

Abstract

Fansimef is a new antimalarial schizontocide that contains mefloquine, pyrimethamine, and sulfadoxine with a weight ratio of 1:20:10. This antimalarial combination is highly active against multidrug-resistant strains of Plasmodium falciparum. H2-receptor antagonists (cimetidine, famotidine, and ranitidine) are reversible competitive blockers of histamine at H2-receptor and do not affect the H1-receptor. These are potent inhibitors of all phases of gastric acid secretion. They do so by binding to H2-receptors on the parietal cells of stomach. The effect of various dissolution mediums with respect to pH on these drug–drug interactions and in vitro availability reveals that availability of antimalarial drugs increased to a smaller extent in the presence of H2-receptors. The influence of temperatures on these interactions has been examined to elucidate the mechanism of these interactions. Antimalarial drugs could be administrated concurrently with H2-receptor antagonist (cimetidine and famotidine); however, ranitidine should not be given because availability was almost suppressed in the presence of antimalarial drugs.