Summary
Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval.
There was considerable intersubject variability in the steady state blood concentrations of chloroquine (range 36.6 to 3895 ng·ml−1) and its two main biotransformation products; the latter represented, respectively, 47.7% and 12.9% of the concentration of chloroquine.
This finding shows the need for further studies in view of the known toxic effects of chloroquine and the inevitable accumulation due to the exceptionally long residence time of the compound and its metabolites. The main requirement, which has not yet been met, for adding chloroquine to the list of drugs for which therapeutic drug monitoring is useful, is the lack of information about its mechanism of action, and consequently the dose-effect relationships of its therapeutic and toxic actions. Regular ophthalmic examination, in particular, is strongly recommended.
The relatively high concentrations of desethylchloroquine and bisdesethylchloroquine found during chronic treatment show the need for more information about the therapeutic value and adverse effects of the metabolites.
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References
Augustijns P (1991) A study of the pharmacokinetic properties of chloroquine and its enantiomers. Ph. D. Thesis, KU Leuven, Belgium
Augustijns P, Verbeke N (1990) HPLC method for the determination of chloroquine and its main metabolite in biological samples. J Liq Chromatogr Clin Analysis 13: 1203–1213
Bellamy N, Brooks PM (1986) Current practice in antimalarial drug prescribing in rheumatoid arthritis. J Rheumatol 13: 551–555
De Vane CL (1980) Tricyclic antidepressants. In: Evans WE, Schentag JJ and Jusko WJ (ed) Applied pharmacokinetics: principles of therapeutic drug monitoring. Applied Therapeutics Inc, San Francisco
Edwards G, Looareesuwan S, Davies AJ, Wattanogoon Y, Phillips RE, Warrell DA (1988) Pharmacokinetics in Thais: plasma and red-cell concentrations following an intravenous infusion to healthy subjects and patients with Plasmodium vivax malaria. Br J Clin Pharmacol 25: 477–485
Essien EE, Ette EI, Thomas WOA, Brown-Awala EA (1989) Chloroquine disposition in hypersensitive and non-hypersensitive subjects and its significance in chloroquine-induced pruritus. Eur J Drug Metab Pharmacokinet 14: 71–77
Essien EE, Ette EI (1986) Effects of chloroquine and didesethylchloroquine on rabbit myocardium and mitochondria. J Pharm Pharmacol 38: 833–840
Frisk-Holmberg M, Bergqvist Y, Domeij-Nijberg B (1983) Steady state disposition of chloroquine in patients with rheumatoid disease. Eur J Clin Pharmacol 24: 837–839
Gustafsson LL, Walker O, Alvan G, Beermann B, Estevez F, Gleissner L, Lindström B (1983) Disposition of chloroquine in man after single intravenous and oral doses. Br J Clin Pharmacol 15: 471–479
Kelly (1989) Textbook of Rheumatology, 3rd ed. Saunders, Philadelphia, p 945
Laaksonen A-L, Koskiahde Juva K (1974) Dosage of antimalarial drugs for children with juvenile rheumatoid arthritis and systemic lupus erythematosus. Scand J Rheumatol 3: 103–108
Mackenzie AH (1983) Antimalarial drugs for rheumatoid arthritis. Am J Med 30: 48–58
Maksymowych W, Russell AS (1987) Antimalarials in rheumatology: efficacy and safety. Semin Arthritis Rheum 16: 206–221
Ofori-Adjei D, Ericsson O, Lindström B, Sjöqvist F (1986) Protein binding of chloroquine enantiomers and desethylchloroquine. Br J Clin Pharmacol 22: 356–358
Rothfield (1988) Efficacy of antimalarials in systemic lupus erythematosus. Am J Med 85 (4A): 53–56
Rynes RI (1985) Antimalarial treatment of rheumatoid arthritis: 1985 status. J Rheumatol 12: 657–659
Titus EO (1989) Recent developments in the understanding of the pharmacokinetics and mechanism of action of chloroquine. Ther Drug Monit 11: 369–379
Walker O, Birkett DJ, Alvan G, Gustafsson LL, Sjöqvist F (1983) Characterization of chloroquine plasma protein binding in man. Br J Clin Pharmacol 15: 375–377
Wolheim FA, Hanson A, Laurell C-B (1978) Chloroquine treatment in rheumatoid arthritis. Scand J Rheumatol 7: 171–176
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Augustijns, P., Geusens, P. & Verbeke, N. Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis. Eur J Clin Pharmacol 42, 429–433 (1992). https://doi.org/10.1007/BF00280130
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DOI: https://doi.org/10.1007/BF00280130