Abstract
1. Ten patients with bilateral knee joint effusions were treated topically with a gel containing 1 g diclofenac/100 g (80 mg three times daily). They were randomized to receive diclofenac gel to one knee and a placebo gel preparation to the other knee. 2. Diclofenac was assayed in synovial fluid and blood plasma by GC/ECD as the pentafluorobenzyl-ester derivative. 3. Total concentrations of diclofenac in synovial fluid (day 4) were significantly higher in the diclofenac gel treated knee than in the contralateral placebo treated knee (25.5 +/- 3.6 ng ml-1 vs 21.6 +/- 2 ng ml-1; P less than 0.05). These concentrations were lower than total plasma drug concentrations (40.6 +/- 4.7 ng ml-1, n = 10, P less than 0.01). Unbound concentrations of diclofenac in synovial fluid from either the diclofenac gel treated or the placebo treated knee were not significantly different from each other or from plasma free concentrations (115 +/- 16 and 99 +/- 12 vs 108 +/- 19 pg ml-1). 4. Clinical parameters showed improvement of joint mobility and a small reduction of swelling (circumference) in both knees with time. However, the differences between knees were not significant. 5. We conclude that direct transport of diclofenac from the skin into the ipsilateral knee joint after cutaneous application is minimal. Distribution seems to be predominantly via the blood. Whether the observed improvements of clinical parameters were due to drug effects or to the spontaneous course of the underlying disease cannot be distinguished.
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Selected References
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- Chan K. K., Vyas K. H., Brandt K. D. In vitro protein binding of diclofenac sodium in plasma and synovial fluid. J Pharm Sci. 1987 Feb;76(2):105–108. doi: 10.1002/jps.2600760204. [DOI] [PubMed] [Google Scholar]
- Fowler P. D., Dawes P. T., John V. A., Shotton P. A. Plasma and synovial fluid concentrations of diclofenac sodium and its hydroxylated metabolites during once-daily administration of a 100 mg slow-release formulation. Eur J Clin Pharmacol. 1986;31(4):469–472. doi: 10.1007/BF00613526. [DOI] [PubMed] [Google Scholar]
- Fowler P. D., Shadforth M. F., Crook P. R., John V. A. Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis. Eur J Clin Pharmacol. 1983;25(3):389–394. doi: 10.1007/BF01037953. [DOI] [PubMed] [Google Scholar]
- Geiger U. P., Degen P. H., Sioufi A. Quantitative assay of diclofenac in biological material by gas-liquid chromatography. J Chromatogr. 1975 Sep 3;111(2):293–298. doi: 10.1016/s0021-9673(00)99277-x. [DOI] [PubMed] [Google Scholar]
- Liauw H. L., Ku E., Brandt K. D., Benson M. D., Aldo-Benson M. A., Waiter S. L., Lee W., Chan K., Vyas K. Effects of Voltaren on arachidonic acid metabolism in arthritis patients. Agents Actions Suppl. 1985;17:195–199. doi: 10.1007/978-3-0348-7720-6_24. [DOI] [PubMed] [Google Scholar]
- Plavsić F., Culig J. Determination of serum diclofenac by high-performance liquid chromatography by electromechanical detection. Hum Toxicol. 1985 May;4(3):317–322. doi: 10.1177/096032718500400313. [DOI] [PubMed] [Google Scholar]
- Riess W., Schmid K., Botta L., Kobayashi K., Moppert J., Schneider W., Sioufi A., Strusberg A., Tomasi M. Die perkutane Resorption von Diclofenac. Arzneimittelforschung. 1986 Jul;36(7):1092–1096. [PubMed] [Google Scholar]
- Riess W., Stierlin H., Degen P., Faigle J. W., Gérardin A., Moppert J., Sallmann A., Schmid K., Schweizer A., Sulc M. Pharmacokinetics and metabolism of the anti-inflammatory agent Voltaren. Scand J Rheumatol Suppl. 1978;(22):17–29. doi: 10.3109/03009747809097212. [DOI] [PubMed] [Google Scholar]
- Todd P. A., Sorkin E. M. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1988 Mar;35(3):244–285. doi: 10.2165/00003495-198835030-00004. [DOI] [PubMed] [Google Scholar]
- Wallis W. J., Simkin P. A. Antirheumatic drug concentrations in human synovial fluid and synovial tissue. Observations on extravascular pharmacokinetics. Clin Pharmacokinet. 1983 Nov-Dec;8(6):496–522. doi: 10.2165/00003088-198308060-00002. [DOI] [PubMed] [Google Scholar]