Summary
The concentration of 6-methoxy-2-naphthylacetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone under steady-state conditions. 6-MNA is the principle metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. Patients suffering from rheumatoid arthritis (n=12) or osteoarthritis stage III or IV (n=8) received a daily dose of nabumetone 1g in the evening starting 4 days prior to surgery. On day 1 an additional loading dose of nabumetone 1g was given in the morning. At the time of surgery (day 5), blood, synovial tissue and fibrous capsule tissue were taken simultaneously. The samples were analysed by high performance liquid chromatography. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 mg/L, in synovial fluid 34.79 mg/L, in synovial tissue 19.33 mg/g and in fibrous capsule tissue 11.43 mg/g. Under steadystate conditions mean synovial fluid levels of 6-MNA were higher than after administration of a single dose and, in common with levels in synovial tissue, persist in a range sufficient for in vitro cyclo-oxygenase inhibition.
Similar content being viewed by others
References
Appclrouth DJ, Bairn S, Chang RW, Cohen MH, England DW, et al. Comparison of the safety and efficacy of nabumetone and aspirin in the treatment of osteoarthritis in adults. American Journal of Medicine 83 (Suppl. 4B): 78–81, 1987
Bachmann F. Correlation of plasma and synovial fluid concentrations of piroxicam in patients with rheumatoid arthritis. In Dessain P (Ed.) Rheumatology in the eighties, pp. 44–51, Excerpta Medica, Princeton, 1980
Benson MD, Aldo-Benson M, Brandt KD. Synovial fluid concentrations of diclofenac in patients with rheumatoid arthritis or osteoarthritis. Seminars in Arthritis and Rheumatology 15 (Suppl. 1): 65–67, 1985
Bernhard GC, Appelrouth DJ, Bankhurst AD, Biundo J, Bockow Bl, et al. Long-term treatment of rheumatoid arthritis comparing nabumetone with aspirin. American Journal of Medicine 83 (Suppl. 4B): 44–49, 1987
Bianchi Porro G, Caruso I, Petrillo M, Montrone F, Price JD. Endoscopic evaluation of the effect of naproxen and nabumetone on gastric and duodenal mucosa. Royal Society of Medicine International Congress and Symposium Series 69: 97–102, 1985
Blechman WJ. Nabumetone therapy of osteoarthritis. American Journal of Medicine 83 (Suppl. 4B): 70–73, 1987
Bourke B, Undre NA, Thawley AR. An investigation into the penetration of nabumetone and its metabolites in the synovial fluid in patients with rheumatoid arthritis. Royal Society of Medicine International Congress and Symposium Series 69: 31–35, 1985
Boyle E, Thomson M, Freeman P, Magnan F. Comparative pharmacology of BRL 14777 and BRL 10720. Beecham Data Base, 1978
Carle WK, Rotman H. General practice study of nabumetone and indomethacin in patients with osteoarthritis. Royal Society of Medicine International Congress and Symposium Series 69: 139–148, 1985
Famaey JP. Correlation of plasma levels, NSAID and therapeutic response. Clinical Rheumatology 4: 124–132, 1985
Fenner H. Transsynovialkinetik und Dosis-Wirkungs-Korrelation bei nicht-steroidalen Antirheumatika. Fortschritte der Medizin 100: 1642–1646, 1982
Fenner H. Pharmacokinetics of piroxicam: new aspects. European Journal of Rheumatology and Inflammation 8: 42–48, 1987
Freeman AM, Undre NA, Thawley AR, Golding DN. Plasma and synovial fluid concentrations of nabumetone and BRL 10720 in patients given nabumetone. Royal Society of Medicine International Congress and Symposium Series 69: 37–42, 1985
Jalava S, Saarimaa H, Anttila M, Sundquist H. Naproxen concentrations in serum, synovial fluid and synovium. Scandinavian Journal of Rheumatology 6: 155–157, 1977
Lussier A, LeBel E. Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin and nabumetone. American Journal of Medicine 83 (Suppl. 4B): 15–18, 1987
Schrader HWv, Buscher G, Dierdorf D, Mügge H, Wolf D. Nabumetone — a novel anti-inflammatory drug: bioavailability after different dosage regimens. International Journal of Clinical Pharmacology 22: 672–676, 1984
Vasey FB, Germain BF, Espinoza LR. Controlled evaluation of nabumetone in the treatment of active adult rheumatoid arthritis. American Journal of Medicine 83 (Suppl. 4B): 55–59, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miehlke, R.K., Schneider, S., Sörgel, F. et al. Penetration of the Active Metabolite of Nabumetone into Synovial Fluid and Adherent Tissue of Patients Undergoing Knee Joint Surgery. Med Toxicol Adverse Drug Exp 40 (Suppl 5), 57–61 (1990). https://doi.org/10.2165/00003495-199000405-00014
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199000405-00014