Willburger R E, Wittenberg R H, Schmidt K, Kleemeyer K S, Peskar B A
Department of Orthopedics, Ruhr University, St. Josef-Hospital, Bochum, Germany.
Acta Orthop Scand. 1998 Jun;69(3):295-300. doi: 10.3109/17453679809000934.
Our aim was to determine the amounts of eicosanoids 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-PGF1alpha, 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-PGF1alpha, 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 cyclooxygenase (CO) and 5-lipoxygenase (5-LO) in blood and synovial tissue.
我们的目的是测定膝关节骨关节炎患者血液和滑膜组织中类花生酸的含量，并研究口服给予两种剂量（50mg，每日2次；200mg，每日2次）替泊沙林3.5天的效果。在口服替泊沙林前后测定血液中白三烯B4（LTB4）、白三烯C4（LTC4）和血栓素B2（TXB2）的浓度，在手术中采集接受替泊沙林治疗患者的滑膜组织，测定其培养介质中前列腺素E2（PGE2）、6-酮-前列腺素F1α（6-keto-PGF1α）和LTC4的释放量。采用放射免疫分析法（RIA）测定类花生酸水平。两种剂量的替泊沙林均可降低LT和TXB2的释放。在此条件下，仅在钙离子载体A23187刺激后才能检测到滑膜组织中PGE2、6-keto-PGF1α和LTC4的释放。与直接培养的滑膜组织相比，洗过的滑膜组织（其中替泊沙林浓度应降低）释放的所有测定类花生酸量更高。服用替泊沙林后的疼痛明显减轻。在血浆和滑液中检测到了相关药物浓度。替泊沙林耐受性良好，无明显不良反应。在血液和滑膜组织中，400mg替泊沙林是一种环氧化酶（CO）和5-脂氧合酶（5-LO）的双重抑制剂。
