DISPOSITION AND ABSORPTION OF HYDROXYCHLOROQUINE ENANTIOMERS FOLLOWING A SINGLE-DOSE OF THE RACEMATE

The disposition of hydroxychloroquine enantiomers has been investigate d in nine patients with rheumatoid arthritis following administration of a single dose of the racemate. Blood concentrations of (-)-(R)-hydr oxychloroquine exceed those of (+)-(S)hydroxychloroquine following bot h an oral and intravenous dose of the racemate. Maximum blood concentr ations of (-)-(R)-hydroxychloroquine were higher than (+)-(S)-hydroxyc hloroquine after oral dosing (121 +/- 56 and 99 +/- 42 ng/ml, respecti vely, P = 0.009). The time to maximum concentration and the absorption half-life, calculated using deconvolution techniques, were similar fo r both enantiomers. The fractions of the dose of each enantiomer absor bed were similar, 0.74 and 0.77 for (-)-(R)- and (+)-(S)-hydroxychloro quine, respectively (P = 0.77). The data suggest that absorption of hy droxychloroquine is not enantioselective. The stereoselective disposit ion of hydroxychloroquine appears to be due to enantioselective metabo lism and renal clearance, rather than stereoselectivity in absorption and distribution. (C) 1994 Wiley-Liss, Inc.