DISPOSITION OF THE ENANTIOMERS OF HYDROXYCHLOROQUINE IN PATIENTS WITHRHEUMATOID-ARTHRITIS FOLLOWING MULTIPLE DOSES OF THE RACEMATE

In eight patients with rheumatoid arthritis receiving racemic hydroxyc hloroquine, blood and urine concentrations of the enantiomers of hydro xychloroquine and its major metabolites were measured each month over the first 6 months of therapy. Plasma concentrations of hydroxychloroq uine enantiomers were measured in five of these patients. In all patie nts, the blood concentration of (R)-hydroxychloroquine exceeded that o f the (S)-enantiomer, the mean (R)/(S) ratio being 2.2 (range 1.6-2.9) . A similar excess of (R)-hydroxychloroquine was found in the plasma, the mean (R)/(S) ratio being 1.6 (range 1.2-1.9). The mean enantiomer blood concentration ratio (R)/(S) for the metabolite desethylhydroxych loroquine was 0.45 (range 0.34-0.58) and for desethylchloroquine it wa s 0.56 (range 0.35-0.86) suggesting stereoselective metabolism of hydr oxychloroquine. (S)-hydroxychloroquine had a mean (+/- s.d.) renal cle arance from blood of 41 +/- 11 ml min-1, approximately twice that of ( R)-hydroxychloroquine. The predicted unbound renal clearance was also higher for (S)-hydroxychloroquine. The clinical implications of enanti oselective disposition of hydroxychloroquine are currently not known.