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Pharmacokinetics and pharmacodynamics of hydroxychloroquine enantiomers in patients with rheumatoid arthritis receiving multiple doses of racemate
Author(s) -
Tett Susan E.,
McLachlan Andrew J.,
Cutler David J.,
Day Richard O.
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060420
Subject(s) - hydroxychloroquine , rheumatoid arthritis , chemistry , pharmacodynamics , enantiomer , pharmacokinetics , pharmacology , arthritis , stereochemistry , medicine , covid-19 , disease , infectious disease (medical specialty)
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 patients, in whom blood and urine concentrations were measured during the first 6 months of therapy with rac‐hydroxychloroquine, and one of 43 patients who had received rac‐hydroxychloroquine therapy for at least 6 months. In the latter study rheumatoid disease activity was also measured. The pharmacokinetics of hydroxychloroquine were found to be enantioselective. 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 clearance were greater for the (+)‐(S)‐enantiomer. From the observational, cross‐sectional study design used, it was not possible to differentiate concentration–effect relationships of the two enantiomers. The 11‐fold range of drug concentrations swamped any effect of variability between patients in enantiomer proportions. Blood concentrations of both enantiomers were significantly higher in groups of patients with less active disease. © 1994 Wiley‐Liss, Inc.