Antiinflammatory effect of tepoxalin Blood and synovial tissue studied in patients with knee arthrosis

Abstract

Our aim was to determine the amounts of eicosan-oids in blood and synovial 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 B₄ (LTB₄), LTC₄, and thromboxane B₂ (TXB₂) were measured in blood before and after oral administration of tepoxalin and release of prostaglandin E₂ (PGE₂), 6-keto-PGF_1alpha, and LTC₄ was measured in incubation media of synovial tissue, taken at surgery from patients treated with tepoxalin. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids.

LT and TXB₂ release was reduced by tepoxalin in both doses used. Under these conditions, PGE₂, 6-keto-PGF_1alpha, and LTC₄ release from synovial tissue was detectable only after stimulation with calcium ionophore A23187. Washed synovial tissue, in which tepoxalin concentrations should be reduced, released higher amounts of all eicosanoids measured 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 tolerated and had no marked adverse effects.

At 400 mg, tepoxalin is a dual inhibitor of cyclo-oxygenase (CO) and 5-lipoxygenase (5-LO) in blood and synovial tissue.