title: Antimalaria activity of the triple combination of proguanil, atovaquone and dapsone.
abstract: The combination of proguanil and atovaquone has been shown to be more effective in curing drug-resistant infections of falciparum malaria than atovaquone or proguanil alone. Our current study sought to determine whether the antimalaria activity could be increased by adding dapsone. Plasma samples, obtained from individuals 4-72 h after proguanil-atovaquone administration, were 2-3 times more active against Plasmodium falciparum in vitro when dapsone was added to them. The enhanced activity of the combination of proguanil, atovaquone and dapsone is probably due to the combined activity of two synergistic combinations: proguanil-atovaquone and cycloguanil (metabolite of proguanil)-dapsone. These findings suggest that further studies are needed to evaluate the clinical value of the triple drug combination of proguanil, atovaquone and dapsone in the treatment of multi-drug resistant malaria.
authors.affiliation: Australian Army Malaria Research Unit, Liverpool Military Area, NSW, Australia. tony_yeo@blackburn.med.su.oz.au
authors.forename: A E
authors.initials: AE
authors.lastname: Yeo
authors.forename: M D
authors.initials: MD
authors.lastname: Edstein
authors.forename: K H
authors.initials: KH
authors.lastname: Rieckmann
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D053626:Atovaquone; D003622:Dapsone / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D009285:Naphthoquinones / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects*; D002727:Proguanil / Q000627:therapeutic use; D013785:Thailand
chemical_list: D000962:Antimalarials; D009285:Naphthoquinones; D003622:Dapsone; D002727:Proguanil; D053626:Atovaquone