Antimalarial drug synergism and antagonism: mechanistic and clinical significance.
Interactions between antimicrobial agents provide clues as to their mechanisms of action and influence the combinations chosen for therapy of infectious diseases. In the treatment of malaria, combinations of drugs, in many cases acting synergistically, are increasingly important in view of the frequency of resistance to single agents. The study of antimalarial drug interactions is therefore of great significance to both treatment and research. It is therefore worrying that the analysis of drug-interaction data is often inadequate, leading in some cases to dubious conclusions about synergism or antagonism. Furthermore, making mechanistic deductions from drug-interaction data is not straightforward and of the many reported instances of antimalarial synergism or antagonism, few have been fully explained biochemically. This review discusses recent findings on antimalarial drug interactions and some pitfalls in their analysis and interpretation. The conclusions are likely to have relevance to other antimicrobial agents.
Bell
Angus
A
Department of Microbiology, Moyne Institute of Preventive Medicine, University of Dublin--Trinity College, Dublin 2, Ireland. abell@tcd.ie
D000818:Animals; D000962:Antimalarials / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005493:Folic Acid Antagonists / Q000494:pharmacology; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000382:microbiology* / Q000517:prevention & control; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D005493:Folic Acid Antagonists; D011480:Protease Inhibitors; D011804:Quinolines; D012717:Sesquiterpenes; C031327:artemisinin