Effects of piperaquine, chloroquine, and amodiaquine on drug uptake and of these in combination with dihydroartemisinin against drug-sensitive and -resistant Plasmodium falciparum strains

Abstract

Piperaquine is being developed as a long-acting component in artemisinin combination therapies. It was highly active in vitro and drug interaction studies showed that dihydroartemisinin combinations with piperaquine, chloroquine, and amodiaquine were indifferent tending toward antagonism. Competitive uptake of radiolabeled chloroquine and dihydroartemisinin in combination with other antimalarials was observed.

FIG. 1.

Effects of antimalarials on the uptake of 2.5 nM [³H]CQ after 90 min in erythrocytes infected with P. falciparum. Each bar represents the average of at least two experiments. An asterisk signifies a statistically significant decrease (P < 0.05) in all four parasite lines compared to drug uptake alone.

FIG. 2.

Effects of antimalarials on the uptake of 3 nM [³H]DHA after 90 min in erythrocytes infected with P. falciparum. Each bar represents the average of at least two experiments. An asterisk signifies a statistically significant decrease (P < 0.05) in all four parasite lines compared to drug uptake alone.