Comparison of the partitioning in vitro of chloroquine and its desethyl metabolites between the erythrocytes and plasma of healthy subjects and those with falciparum malaria.

The partitioning of chloroquine and its two desethyl metabolites between red blood cells (RBCs) and plasma was studied in vitro, using blood from healthy adults and from children with Plasmodium falciparum parasitaemia. Blood from the volunteers was incubated with varying concentrations of chloroquine (CQ), desethylchloroquine (DCQ) and bisdesethyl-chloroquine (BDCQ) for 15 min and the RBC/plasma concentration ratio determined. Desethylchloroquine and BDCQ were concentrated in the red cells of uninfected blood to the same extent as chloroquine. On the other hand, DCQ and BDCQ were concentrated to a significantly lower extent than CQ in the red cells from malarial children. The reduced ability of infected RBCs to concentrate DCQ and BDCQ may have an important bearing on the development of resistance to chloroquine by P. falciparum.