Pharmacokinetic aspects of chloroquine-induced pruritus: influence of dose and evidence for varied extent of metabolism of the drug.

The significance of a pharmacokinetics basis in chloroquine (CQ)-induced pruritus was investigated by determining the disposition of the drug in two groups of volunteers; pruritus positive and pruritus negative. Single oral dose of 600 mg CQ was administered to each of 36 volunteers, 18 for each of the two groups. After a washout period of 9 months, 150 mg single oral dose of the drug was given to 12 of the same volunteers, six each from the two groups. Blood and urine samples were collected at predetermined times following administration of each dose. Concentrations of CQ and its major metabolite, desethylchloroquine (CQM), were measured in plasma and urine using an established HPLC method. Results showed that the ratio, AUC (CQ)/AUC (CQM), as well as AUC(0-48 h) and 24-h urinary CQ excretion were all significantly higher (P<0.05) in pruritus-positive compared to pruritus-negative volunteers, following administration of the 600-mg CQ dose. Also, urinary drug-metabolite ratios monitored over 0-48 h postdose were markedly higher in the pruritus positive group. However, after administration of the 150-mg dose, 24-h urinary CQ collection and urinary drug-metabolite ratios were highly comparable between the two groups (P>0.1). This study indicates that there might be a decreased metabolism of CQ in subjects susceptible to CQ-induced pruritus following ingestion of a therapeutic dose. It also suggests that the extent of metabolism of CQ in this group may be influenced by the dose of the drug. Comparatively higher CQ levels in pruritus susceptible subjects may possibly be responsible for the pruritus experienced by such individuals when given therapeutic regimen.