Diclofenac sodium (Voltaren") is a non-steroid anti-inflammatory agent of a new chemical structure, which in animal experiments shows a high degree of antiinflammatory, analgesic, and antipyretic activity in various pharmacological models. It inhibits prostaglandin biosynthesis in vitro and in vivo, and this inhibitory effect at least partly explains the mechanism of action of the preparation. In animal experiments diclofenac sodium is characterised by a broad therapeutic range. Also, its gastrointestinal tolerability is better than that of other highly effective non-steroid anti-inhmmatory agents. Two of the metabolites produced during the biotransformation of diclofenac sodium in man are also biologically active. The activity of these two metabolites, however, is very much weaker than that of unchanged diclofenac sodium and is comparable to that of phenylbutazone. S a n d J Rheumutology, Suppl. 22 Scand J Rheumatol Downloaded from informahealthcare.com by University of Guelph on 10/19/12 For personal use only. Scand J Rheumatology. Suppl. 22 Scand J Rheumatol Downloaded from informahealthcare.com by University of Guelph on 10/19/12 For personal use only. Scand J Rheurnatology. Suppl. 22 Scand J Rheumatol Downloaded from informahealthcare.com by University of Guelph on 10/19/12 For personal use only. 'I Dose leading to a blood loss of IS0 wl/72 h. ' ' No effect observed at this dose level. ' Marginal. though statistically significant, increase over the control level observed at 300 mg/kg p.0. '' No mortality observed at this dose level. Metabolite I M > I 0 0 18 M 240 (203-287) 70 70 60 60 70 70 20 50Scand J Rheumatol Downloaded from informahealthcare.com by University of Guelph on 10/19/12For personal use only.

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In rats with adjuvant arthritis, an analysis was made of the metabolism of sulfated proteoglycans, with particular attention to the dorsal skin and the extremities. Alterations were demonstrated in all the tissues examined. In the uninflamed dorsal skin, the uptake of exogenous sulfate was diminished. By contrast, in both hind limbs, at the injected and the non-injected site, the turnover of sulfated mucopolysaccharides was increased, above all in ligament and cartilage; the calcium content of the bone tissue of both hind legs was, however, not affected by the disease.

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