Increased accumulation of chloroquine and desethylchloroquine in homozygous sickle cells.

The effect of haemoglobin genotype on the level of chloroquine in the erythrocytes of homozygous sickle-cell (SS), normal (AA), and heterozygous (AS) subjects was investigated in vivo and in vitro. Two hours after a single oral dose of chloroquine its level in plasma was consistently lower in SS than in AA subjects. In contrast, its level in the erythrocytes was higher in SS than in AA subjects. Desethylchloroquine, a metabolite of chloroquine, was detected only in the erythrocytes of SS blood but was present in both the plasma and erythrocytes of AA blood. For the in vitro test, a 5% suspension of erythrocytes was incubated for 1 hour with a 2.06 mumol/l solution of chloroquine. The mean chloroquine distribution ratio (mumol chloroquine per kg erythrocytes:mumol chloroquine per litre medium) was 31.0, 3.5, and 2.7 for SS, AA, and AS erythrocytes, respectively. The results of the study indicate that haemoglobin genotype appears to influence the level of chloroquine in erythrocytes.