Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine.
Plaquenil (hydroxychloroquine, HCQ; Sanofi Winthrop Pharmaceuticals, New York, NY) is a stereoisomeric drug administered as a racemic (50: 50) mixture of two isomeric forms--(+) and (-) HCQ. To correlate clinical efficiency accurately with dose, it is necessary to determine the fate of both isomers. This will allow for the optimization of clinical dosing. A method has been developed for the quantitation of (+) and (-) HCQ and its major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), in plasma and in urine. Application of this method in a preliminary study in four human volunteers is reported. After a single oral dose of 200 mg of Plaquenil, the average enantiomeric ratio of (+) to (-) HCQ was approximately 1 over an 8-hour period. However, the average cumulative 48-hour excretion of HCQ, DHCQ, and DCQ showed stereoselective excretion.
Iredale
J
J
Department of Oncology, McGill University, Montreal General Hospital, Quebec, Canada.
Fieger
H
H
Wainer
I W
IW
D002738:Chloroquine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D006886:Hydroxychloroquine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D013237:Stereoisomerism; D013997:Time Factors
D006886:Hydroxychloroquine; D002738:Chloroquine; C007278:desethylchloroquine