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© 1988 British Society for Rheumatology

research-article

NAPROXEN DOSE AND CONCENTRATION: RESPONSE RELATIONSHIP IN RHEUMATOID ARTHRITIS

F. M. DUNAGAN1, P. E. McGILL2,, A. W. KELMAN3,4 and B. WHITING1

1Departments of Materia Medica Stobhill General Hospital, Glasgow G21 3UW
2Rheumalology Stobhill General Hospital, Glasgow G21 3UW
3Nuclear Medicine Stobhill General Hospital, Glasgow G21 3UW
4Department of Clinical Physics and Bioengineering,West of Scotland Health Boards II West Graham Street, Glasgow, UK

Correspondence to: Address correspondence to Dr. P. E. McGill.

Information on the relationship between the plasma concentration of nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical response in rheumatoid arthritis is sparse. As a result treatment is often relatively empirical. Standard doses are prescribed and an apparent lack of response leads either to the prescription of another drug, or an increase in the dose beyond that recommended.

This study investigated 18 patients given three doses (500, 1000 and 1500 mg/day) of naproxen in a randomized double-blind design for 12 days at a time. Using a linear modelling approach we found that three out of four clinical response measurements improved linearly with increasing naproxen trough concentrations, suggesting that most patients will achieve an improvement in symptoms if the dose of naproxen is increased up to 1500 mg/day. However, since trough naproxen concentrations show a less than proportional increase with increasing dose (due to saturation of binding sites on plasma albumin), the improvement in response will be less dramatic as the dose is increased.

KEY WORDS: NSAID, Rheumatoid arthritis, Naproxen, Concentration-effect relationship


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