The effect of artesunate combined with standard antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro.
The interactions of artesunate with chloroquine, mefloquine, quinine, doxycycline and pyrimethamine were tested in vitro against chloroquine-sensitive (D10) and chloroquine-resistant (RSA11) strains of Plasmodium falciparum. Mefloquine and quinine both showed synergism of artesunate activity against each of the strains, whilst doxycycline showed an additive interaction. Pyrimethamine combinations were antagonistic, and the combination of artesunate with chloroquine was antagonistic against RSA11, and additive against D10. Although weak antagonism in vitro might not indicate any clinical significance, synergism with artesunate may increase the clinical usefulness of either drug, and could potentially be of value in delaying the emergence of resistance.
Fivelman
Q L
QL
Department of Pharmacology, University of Cape Town, Medical School, South Africa.
Walden
J C
JC
Smith
P J
PJ
Folb
P I
PI
Barnes
K I
KI
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D000077332:Artesunate; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D015767:Mefloquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D000077332:Artesunate; D002738:Chloroquine; D015767:Mefloquine