DISTRIBUTION OF THE ENANTIOMERS OF HYDROXYCHLOROQUINE AND ITS METABOLITES IN OCULAR-TISSUES OF THE RABBIT AFTER ORAL-ADMINISTRATION OF RACEMIC-HYDROXYCHLOROQUINE

The disposition of the enantiomers of hydroxychloroquine (HCQ) and its major metabolites in ocular tissues of rabbits has been studied. Both albino, New Zealand White (NZW), and pigmented animals were administe red daily oral doses of rac-HCQ, (S)-HCQ or (R)-HCQ (20 mg/kg) over 1, 6, or 8 day periods or for 8 days followed by a 7-day washout period. At the end of the study periods, plasma and whole blood samples were collected and the rabbits were sacrificed. The eyes were collected, th e aqueous humor removed with a syringe, and the eyes separated into th e cornea, lens, vitreous body, iris, choroid-retina, sclera, and conju nctiva. The concentrations of (R)-HCQ, (S)-HCQ, and their respective m etabolites were determined using a validated enantioselective liquid c hromatographic assay. The data from these studies indicate that HCQ ac cumulated in both pigmented and nonpigmented ocular tissues. In the pi gmented tissues, HCQ and its metabolites were bound to melanin and the binding was not enantiospecific. In the nonpigmented tissues and in t he iris and retina-choroid of the NZW rabbits, the accumulation appear ed to be the result of a reversible and enantioselective binding of HC Q and its metabolites to an unidentified biopolymer present in these o cular tissues. (C) 1994 Wiley-Liss, Inc.