Anti-prostaglandin and anti-inflammatory short-term efficacy of piroxicam in rheumatoid arthritis.
The efficacy of anti-inflammatory agents is related to their concentration in the peripheral compartments. In rheumatoid arthritis a drug's affinity for synovial tissue and synovial fluid is a decisive factor in treatment. The short-term efficacy of piroxicam was studied, relating the synovial concentration of prostaglandins and acid phosphatase and LDH to piroxicam synovial and plasma levels. After withdrawal of synovial fluid for pre-treatment measurements, 10 patients received 20 to 30 mg of piroxicam/day for eight days. The drug reached an average level of 3.56 +/- 0.9 micrograms/ml in synovial fluid, and 7.73 +/- 1.6 micrograms/ml in plasma. The acid phosphatase decreased from an initial average level of 29 mu/ml to a final average level of 15.999 mu/ml. The LDH showed an initial average level of 725.3 mu/ml and a final average of 471.2 mu/ml (p less than 0.01). The prostaglandin levels were quantified by two methods: indirectly, by measuring the malonilaldehyde concentration in nMol/ml, which showed an average level decrease of 48.75% in 100% of the cases; and directly, by means of thin layer chromatography and biological assay on rats' gastric fundus, against controls. The disappearance of PGE1 and a significant decrease in PGF2 alpha (100%) were observed. We conclude that piroxicam is an effective drug for the short-term treatment of rheumatoid arthritis. It penetrates rheumatoid synovial fluid, reaching 50% plasma concentrations. It has an anti-prostaglandin action, and could stabilize lysosomal membrane.
D000135:Acid Phosphatase / Q000378:metabolism; D000328:Adult; D000527:Alprostadil; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015237:Dinoprost; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008875:Middle Aged; D010894:Piroxicam; D011448:Prostaglandin Antagonists / Q000627:therapeutic use*; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D013843:Thiazines / Q000097:blood / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D011460:Prostaglandins F; D013843:Thiazines; D010894:Piroxicam; D015237:Dinoprost; D007770:L-Lactate Dehydrogenase; D000135:Acid Phosphatase; D000527:Alprostadil