|The effects of diclofenac sodium on arachidonic acid metabolism.
|Year of Publication
|Ku EC, Lee W, Kothari HV, Kimble EF, Liauw L, Tjan J
|Semin Arthritis Rheum
|2 Suppl 1
|6-Ketoprostaglandin F1 alpha, Animals, Arachidonic Acid, Arachidonic Acids, Chemotaxis, Leukocyte, Cyclooxygenase Inhibitors, Diclofenac, Dinoprostone, Humans, Hydroxyeicosatetraenoic Acids, Ibuprofen, Indomethacin, Leukocytes, Lipoxygenase, Naproxen, Phospholipases A, Phospholipases A2, Phospholipids, Piroxicam, Prostaglandins E, SRS-A, Thiazines, Triglycerides
Evidence has been presented that inhibition by diclofenac sodium of the production of leukotrienes by cells participating in the inflammatory process is due to a decreased availability of intracellular arachidonic acid which results from enhanced uptake of the substrate into triglyceride pools. The diminished leukotriene production does not result from direct inhibition of 5-lipoxygenase or phospholipase A2. Reduced availability of arachidonic acid would also limit production of prostaglandins, although in this case manifestation is obscured by the potent inhibitory effect of diclofenac sodium on cyclooxygenase. This recently discovered action of diclofenac sodium, which has been characterized by studies on isolated leukocytes, appears to be operative in vivo. Consistent with this mechanism, and not explainable by classical cyclooxygenase inhibition, diclofenac sodium inhibited leukotriene production in whole blood from drug-treated animals and also suppressed leukocyte infiltration of subcutaneously implanted sponges. The latter effect contrasts with increased infiltration frequently obtained with other NSAIDs and thought to reflect enhanced production of leukotrienes. In conclusion, the findings suggest that patient acceptance or preference for diclofenac sodium is not merely subjective but has a logical scientific basis.
|Semin. Arthritis Rheum.