Twenty-one healthy Nigerian volunteers distributed into four groups participated in a study to determine the significance of
chloroquine disposition in
chloroquine-induced
pruritus. It involved the administration of
chloroquine with or without
promethazine pre-administration to the subjects. Group I consisted of 8
chloroquine non-hypersensitive subjects receiving 2
tablets of
chloroquine sulphate (300 mg base); Group II consisted of 5
chloroquine non-hypersensitive subjects receiving 2
tablets of
chloroquine sulphate 30 minutes after 25 mg
promethazine tablet pre-administration; Group III consisted of 5
chloroquine hypersensitive subjects treated as in Group II; Group IV consisted of 3 hypersensitive subjects treated as in Group I. Blood (5 ml) and urine samples were collected periodically for up to 6 days post-dose. The samples were analysed for
chloroquine and some of its oxidation metabolites by a specific HPLC method. Probit plots of cumulative
drug/metabolite ratios were done to determine if there is polymorphism in
chloroquine metabolism. There was bimodality only in the distribution of
chloroquine/
monodesethylchloroquine ratios, suggesting polymorphism in the metabolic oxidation of
chloroquine in these subjects. Higher levels of
monodesethylchloroquine were obtained in Group IV subjects when compared with any of the other groups. The oral clearance rate, elimination half-life, and volume distribution at steady state of
chloroquine in the study groups were not significantly different (P greater than 0.05). In the absence of
promethazine there appears to be an extensive metabolism of
chloroquine in hypersensitive individuals to produce
monodesethylchloroquine which probably determines the degree of
pruritus experienced by an individual.