Summary
The in vitro binding of the enantiomers of hydroxychloroquine and its three major metabolites in pooled plasma obtained from four healthy volunteers and the binding of the enantiomers of hydroxychloroquine to purified plasma proteins has been investigated.
The plasma protein binding of hydroxychloroquine was found to be stereoselective. The (S)-enantiomer of hydroxychloroquine was 64% bound in plasma, while (R)-hydroxychloroquine was 37% bound. Fifty % of (S)-hydroxychloroquine was bound to a 40 g·l−1 solution of human serum albumin, while only 29% of the (R)-enantiomer was bound. The enantioselectivity of hydroxychloroquine binding was reversed in a 0.7 g·l−1 solution of α1-acid glycoprotein with (R)-hydroxychloroquine being bound to a greater extent than its optical antipode (41% versus 29%). The enantiomers of the 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 concentration range of 50 to 1000 ng·ml−1 and hydroxychloroquine metabolite binding to plasma was linear over the range 25 to 500 ng·ml−1.
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References
Geary TG, Akood MA, Jensen JB (1983) Characteristics of chloroquine binding to glass and plastic. Am J Trop Med Hyg 32: 19–23
Gibaldi DA, Perrier D (1982) Pharmacokinetics, 2nd edn. Dekker, New York
Levy RH, Boddy AV (1991) Stereoselectivity in pharmacokinetics: a general theory. Pharm Res 8: 551–555
McLachlan AJ, Tett SE, Cutler DJ (1991) High-performance liquid chromatographic separation of the enantiomers of hydroxychloroquine and its major metabolites in biological fluids using α1-acid glycoprotein stationary phase. J Chromatogr 570: 119–127
Miller DR, Khalil SRW, Nygan GA (1991) Steady-state pharmacokinetics of hydroxychloroquine in rheumatoid arthritis patients. Ann Pharmacother 25: 1302–1305
Ofori-Adjei D, Ericsson O, Lindstrom B, Sjöqvist F (1986) Protein binding of chloroquine enantiomers and desethylchloroquine. Br J Clin Pharmacol 22: 356–358
Piafsky KM, Borgä O (1977) Protein binding of basic drugs. II. Importance of α1-acid glycoprotein for individual variation. Clin Pharmacol Ther 22: 545–549
Piafsky KM, Borgä O, Odar-Cederloe I, Johnsson C, Sjöqvist F (1978) Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma α1-acid glycoprotein. New Eng J Med 299: 1435–1439
Piafsky KM (1980) Disease-induced changes in the plasma binding of basic drugs. Clin Pharmacokinet 5: 246–262
Routledge PA (1986) The plasma protein binding of basic drugs. Br J Clin Pharmacol 22: 499–506
Skeith KJ, Jamali F (1991) Clinical pharmacokinetics of drugs used in juvenile arthritis. Clin Pharmacokinet 21: 129–149
Tett SE, Cutler DJ, Day RO, Brown KF (1988) Dose-ranging study of the pharmacokinetics of hydroxychloroquine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 26: 303–313
Tett SE, Cutler DJ, Day RO (1990a) Hydroxychloroquine concentrations and clinical effects in rheumatoid arthritis patients. Eur J Pharmacol 183: 1035
Tett SE, Cutler DJ, Day RO (1990b) Antimalarials in rheumatic diseases. In: Brooks PM (ed) Bailliere's clinical rheumatology. Slowacting antirheumatic drugs and immunosuppressives. Baillière, Tindall, Sydney, pp 467–489
Tucker GT, Lennard MS (1990) Enantiomer specific pharmacokinetics. Pharmac Ther 45: 309–329
Walker O, Birkett DJ, Alván G, Gustafsson LL, Sjöqvist F (1983) Characterization of chloroquine plasma protein binding in man. Br J Clin Pharmacol 15: 375–377
Williams KM, Lee EJD (1985) Importance of drug enantiomers in clinical pharmacology. Drugs 30: 333–354
Yahya AM, McElnay JC, D'Arcy PF (1986) Investigation of chloroquine binding to plastic materials. Int J Pharm 34: 137–143
Zini R, Riant P, Barré J, Tillement J-P (1990) Disease induced variations in plasma protein levels: implications for drug dosage regimens (I). Clin Pharmacokinet 19: 147–159
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McLachlan, A.J., Cutler, D.J. & Tett, S.E. Plasma protein binding of the enantiomers of hydroxychloroquine and metabolites. Eur J Clin Pharmacol 44, 481–484 (1993). https://doi.org/10.1007/BF00315548
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DOI: https://doi.org/10.1007/BF00315548