PLASMA-PROTEIN BINDING OF THE ENANTIOMERS OF HYDROXYCHLOROQUINE AND METABOLITES

The in vitro binding of the enantiomers of hydroxychloroquine and its three major metabolites in pooled plasma obtained from four healthy vo lunteers and the binding of the enantiomers of hydroxychloroquine to p urified plasma proteins has been investigated. The plasma protein bind ing of hydroxychloroquine was found to be stereoselective. The (S)-ena ntiomer of hydroxychloroquine was 64 % bound in plasma, while (R)-hydr oxychloroquine was 37 % bound. Fifty % of (S)-hydroxychloroquine was b ound to a 40 g . l-1 solution of human serum albumin, while only 29 % of the (R)-enantiomer was bound. The enantioselectivity of hydroxychlo roquine binding was reversed in a 0.7 g . l-1 solution of alpha1-acid glycoprotein with (R)-hydroxychloroquine being bound to a greater exte nt than its optical antipode (41 % versus 29 %). The enantiomers of th e metabolites of hydroxychloroquine were bound to a similar extent to plasma and purified plasma proteins. Binding of hydroxychloroquine to plasma and purified proteins was found to be linear over the racemic c oncentration range of 50 to 1 000 ng . ml-1 and hydroxychloroquine met abolite binding to plasma was linear over the range 25 to 500 ng . ml- 1.