PHARMACOKINETICS AND PHARMACODYNAMICS OF HYDROXYCHLOROQUINE ENANTIOMERS IN PATIENTS WITH RHEUMATOID-ARTHRITIS RECEIVING MULTIPLE DOSES OF RACEMATE

Hydroxychloroquine, a slow acting antirheumatic drug, is administered as the racemic mixture. Blood concentrations of the two enantiomers of hydroxychloroquine were measured in two studies, one study of eight p atients, in whom blood and urine concentrations were measured during t he first 6 months of therapy with rac-hydroxychloroquine, and one of 4 3 patients who had received rac-hydroxychloroquine therapy for at leas t 6 months. In the latter study rheumatoid disease activity was also m easured. The pharmacokinetics of hydroxychloroquine were found to be e nantioselective. The concentrations of (-)-(R)-hydroxychloroquine were higher than those of the (+)-(S)-antipode in all patients at all time points, although the ratios of the two enantiomers did display a two to three fold variability between patients. Both total and renal clear ance were greater for the (+)-(S)-enantiomer. From the observational, cross-sectional study design used, it was not possible to differentiat e concentration-effect relationships of the two enantiomers. The 11-fo ld range of drug concentrations swamped any effect of variability betw een patients in enantiomer proportions. Blood concentrations of both e nantiomers were significantly higher in groups of patients with less a ctive disease. (C) 1994 Wiley-Liss, Inc.