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

The significance of a pharmacokinetics basis in chloroquine (CQ)-induced pr uritus was investigated by determining the disposition of the drug in two g roups of volunteers; pruritus positive and pruritus negative. Single oral d ose 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 follo wing administration of each dose. Concentrations of CQ and its major metabo lite, 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 AUG(0-48 h) and 24-h urinary CQ excretion were all significant ly higher (P <0.05) in pruritus-positive compared to pruritus-negative volu nteers, following administration of the 600-mg CQ dose. Also. urinary drug- metabolite ratios monitored over 0-48 h postdose were markedly higher in th e 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 ther e might be a decreased metabolism of CQ in subjects susceptible to CQ-induc ed pruritus following ingestion of a therapeutic dose. It also suggests tha t the extent of metabolism of CQ in this group may be influenced by the dos e of the drug. Comparatively higher CQ levels in pruritus susceptible subje cts may possibly be responsible for the pruritus experienced by such indivi duals when given therapeutic regimen. (C) 2001 Published by Elsevier Scienc e B.V.