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In vitro assessment of the antimalarial activity of chloroquine and its major metabolites.

A quantitative assessment of the antimalarial activity of chloroquine and its two major metabolites, desethylchloroquine (DEC) and bis-desethylchloroquine (bis-DEC), was made using a semi-automated microdilution technique. Two isolates of Plasmodium falciparum were used: the multi-drug resistant Vietnam Smith LA 137 strain and the chloroquine-sensitive Camp LA 137 strain. Mefloquine served as the standard for the Vietnam Smith strain and chloroquine for the Camp strain. Chloroquine and DEC demonstrated nearly equivalent activities in their inhibition of the growth of the chloroquine-sensitive Camp strain. Bis-DEC was less active since its ID50 was more than twice that of chloroquine. Against the chloroquine-resistant Vietnam Smith strain, DEC showed a three-fold loss of activity and bis-DEC showed no activity at concentrations as high as 340 ng ml-1. A combination of chloroquine and DEC showed an additive effect against both the Vietnam Smith and Camp strains.