SINGLE-DOSE PHARMACOKINETICS OF CHLOROQUINE AND ITS MAIN METABOLITE IN HEALTHY-VOLUNTEERS

The pharmacokinetic properties of chloroquine are still under debate. To establish the pharmacokinetics of a single dose of chloroquine and its metabolites, 19 healthy volunteers, including one Black and one al bino subject, received a single dose of chloroquine 600mg. In addition , one participant also received an oral dose of de-ethylchloroquine 15 0mg. Blood and saliva samples were obtained up to 77 days after drug a dministration. High-performance liquid chromatography was used to meas ure the concentrations of chloroquine, de-ethylchloroquine and bis-de- ethylchloroquine. The mean volume of distribution (Vd), elimination ha lf-life (t1/2) and clearance (CL) of chloroquine were 411 L/kg, 432 ho urs and 0.77 L/h/kg, respectively. For de-ethylchloroquine these value s were 161 L/kg, 649 hours and 0.18 L/h/kg. The results of the Black a nd albino subject were similar. When 150mg of this compound was admini stered, the Vd of deethylchloroquine was 122 L/kg, t1/2 was 529 hours and CL was 0.16 L/h/kg. Bis-de-ethylchloroquine was detectable in 6 vo lunteers. No evidence for a bimodal distribution of chloroquine elimin ation was found in this study. Concentrations of chloroquine in saliva in the terminal elimination phase were 3-fold higher than in plasma.