ANTIINFLAMMATORY EFFECT OF TEPOXALIN - BLOOD AND SYNOVIAL TISSUE STUDIED IN PATIENTS WITH KNEE ARTHROSIS

Our aim was to determine the amounts of eicosanoids in blood and synov ial tissue of patients with knee arthrosis and to examine the effects of 2 doses of tepoxalin (50 mg twice, 200 mg twice), administered p.o. for 3.5 days. Concentrations of leukotriene B-4 (LTB4), LTC4, and thr omboxane B-2 (TXB2) were measured in blood before and after oral admin istration of tepoxalin and release of prostaglandin E-2, (PGE(2)), 6-k eto-PGF(1alpha), and LTC4 was measured in incubation media of synovial tissue, taken at surgery from patients treated with tepoxalin, Radioi mmunoassay (RIA) was used to determine the levels of the eicosanoids. LT and TXB2, release was reduced by tepoxalin in both doses used. Unde r these conditions, PGE(2), 6-keto-PGF(1alpha), and LTC4 release from synovial tissue was detectable only after stimulation with calcium ion ophore A23187. Washed synovial tissue, in which tepoxalin concentratio ns should be reduced, released higher amounts of all eicosanoids measu red than directly incubated synovial tissue did. Pain after tepoxalin administration was significantly reduced. Relevant drug concentrations were detected in plasma and synovial fluid. Tepoxalin was well tolera ted and had no marked adverse effects. At 400 mg, tepoxalin is a dual inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) in blood an d synovial tissue.