UPTAKE AND EFFLUX OF CHLOROQUINE BY CHLOROQUINE-RESISTANT PLASMODIUM-FALCIPARUM CLONES RECENTLY ISOLATED IN AFRICA

In recently isolated African Plasmodium falciparum clones, the intracellular chloroquine concentration at steady-state, under standard culture conditions, could not differentiate chloroquine-sensitive from resistant parasites. However, under an atmosphere of air the chloroquine-resistant P. falciparum clones released pre-accumulated [H-3]chloroquine more rapidly than sensitive clones. The very fast efflux of the preaccumulated drag from chloroquine-resistant (CQR) parasites resulted in a differential in the drug retained by resistant and sensitive parasites. The chloroquine-sensitive parasites retained 2-3 times more chloroquine than resistant parasites. The steady-state uptake of [H-3]chloroquine appeared to be enhanced by verapamil and desipramine in the chloroquine-resistant clones, while the opposite was observed with sensitive clones. This confirmed the suggestion that verapamil inhibits the rapid efflux in CQR parasites resulting in a readily detectable increase in chloroquine accumulation. These observations indicate that the biochemical phenotypes of African chloroquine-resistant P. falciparum are similar to those reported from S.E. Asia and Latin America and are consistent with a common molecular basis for the phenomenon.