Chloroquine resistance is not associated with drug metabolism in Plasmodium falciparum

Chloroquine-sensitive and -resistant clones of Plasmodium falciparum were incubated in vitro with [³H]chloroquine for 16 hr, and the resulting culture supernatants and cell pellets were analyzed by high-performance liquid chromatography for evidence of chloroquine metabolism. After separation by normal- or reverse-phase chromatography, there was no evidence of drug metabolism by the chloroquine-resistant P. falciparum. However, a single, unidentified, radiolabeled metabolite, which did not coelute with desethylchloroquine, was produced by 1 of the chloroquine-sensitive clones. Thus, chloroquine resistance does not appear to be due to drug metabolism by the resistant parasites.