E-DRUG: Chloroquine therapeutic levels (2)
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Dear Annoesjka,
We have done some work in this area, with hydroxychloroquine, but have
also reviewed chloroquine, as follows
Tett S. Clinical pharmacokinetics of slow acting antirheumatic drugs.
Clinical Pharmacokinetics, 25 (1993) 392-407.
Tett SE & Cutler DJ. Apparent dose dependence of chloroquine
pharmacokinetics due to limited assay sensitivity and short sampling
protocols. European Journal of Clinical Pharmacology, 31 (1987) 729-31.
McLachlan A, Tett S, Day R & Cutler D. Interpretation of chloroquine
pharmacokinetic data. (letter) European Journal of Clinical Pharmacology,
44 (1993) 407-8.
Some of our work with hydroxychloroquine includes
Tett SE, Day RO & Cutler DJ. Concentration-effect relationship of
hydroxychloroquine in rheumatoid arthritis - a cross-sectional study.
Journal of Rheumatology, 20 (1993) 1874-9.
Tett SE, Cutler DJ, Day RO & Brown KF. A dose-ranging study of the
pharmacokinetics of hydroxychloroquine following intravenous
administration to healthy volunteers. British Journal of Clinical
Pharmacology, 26 (1988) 303-13.
Tett SE, Cutler DJ, Day RO & Brown KF. Bioavailability of
hydroxychloroquine tablets in healthy volunteers. British Journal of
Clinical Pharmacology, 27 (1989) 771-9.
Tett SE, Cutler DJ & Day RO. Bioavailability of hydroxychloroquine
tablets assessed using deconvolution techniques. Journal of
Pharmaceutical Sciences, 81 (1992) 155-159.
McLachlan AJ, Tett SE, Cutler DJ & Day RO. Bioavailability and in vivo
dissolution of hydroxychloroquine tablets assessed using deconvolution
techniques in fed volunteers. British Journal of Clinical Pharmacology,
36 (1993) 405-11.
McLachlan A, Tett S, Cutler D & Day R. Bioavailability of
hydroxychloroquine tablets in patients with rheumatoid arthritis.
British Journal of Rheumatology, 33 (1994) 235-9.
Tett SE, Day RO, Cutler DJ. Hydroxychloroquine relative
bioavailability: within subject reproducibility. British Journal of
Clinical Pharmacology, 41 (1996) 244-6.
** NB. We have not done any work with children.
In adults with rheumatoid arthritis, receiving hydroxychloroquine
chronically (200 or 400 mg of the sulphate salt per day) we have
measured steady-state whole blood trough concentrations of between 200
and 1200 ng/mL (0.02 and 0.12 mg/100mL).
Frisk-Holmberg and Bergqvist from Sweden have published more on
chloroquine concentrations. Their papers are referenced in our
publications. They have also published something on concentrations after
overdose (sorry, I can't remember the reference - you could find it
perhaps with a Medline - I think it was in the European Journal of
Clinical Pharmacology).
Whole blood concentrations are much more reproducible than plasma
concentrations. Specific assays (eg. HPLC) are most helpful, as
metabolite concentrations may also be quite high.
Hope this helps
Sue Tett
Assoc Prof Susan Tett
Head, School of Pharmacy
The University of Queensland
Brisbane QLD 4072
Ph: 61-7-3365-3191
FAX: 61-7-3365-1688
email: s.tett@pharmacy.uq.edu.au
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