Willburger R E, Wittenberg R H, Kleemeyer K S, Hoos R, Brunner-Ferber F L, Peskar B A
Dept. of Orthopaedic Surgery, St. Josef-Hospital, Ruhr University, Bochum, Germany.
Prostaglandins. 1996 Oct;52(4):327-38. doi: 10.1016/s0090-6980(96)80001-h.
The pharmacological profile of a novel dual inhibitor, tepoxalin and of its carboxylic acid metabolite on cyclooxygenase and lipoxygenase pathways was evaluated by in vitro incubation with synovial tissue. Tissue specimens obtained at surgery in rheumatoid arthritis (RA, n = 10) or osteoarthritis (OA, n = 11) patients were incubated. Tepoxalin (10(-7), 10(-6), 10(-5) M) decreased eicosanoid release calculated in % of tyrode control for OA: LTC4 to 71-33%, 6-keto-PGF1a to 37-20%, PGE2 to 29-6%. For RA: LTC4 to 56-22%, 6-keto-PGF1a to 43-22%, PGE2 to 57-32%. Similarly, its metabolite (10(-7), 10(-5)M) decreased release in OA: LTC4 to 99 and 60%, PGE2 to 42 and 20%, 6-keto-PGF1a to 54 and 25%. In RA:LTC4 to 81 and 45%, PGE2 to 61 and 30%, 6-keto-PGF1a to 46 and 18%. Significance (P < 0.05) was achieved for all but 1 group (LTC4 metabolite at 10(-7)M vs tyrode). In summary a marked and dose dependent decrease of LT and PG release was obtained when incubating the dual inhibitor tepoxalin and its active carboxylic acid metabolite with synovial tissue at doses expected to be reached in the joint during therapy.
通过与滑膜组织进行体外孵育，评估了新型双重抑制剂替泊沙林及其羧酸代谢物在环氧合酶和脂氧合酶途径上的药理学特性。对类风湿性关节炎（RA，n = 10）或骨关节炎（OA，n = 11）患者手术时获取的组织标本进行孵育。替泊沙林（10⁻⁷、10⁻⁶、10⁻⁵ M）使OA中类花生酸释放量相对于泰罗德对照的百分比降低：白三烯C4（LTC4）降至71 - 33%，6 - 酮 - 前列环素F1α（6 - keto - PGF1α）降至37 - 20%，前列腺素E2（PGE2）降至29 - 6%。对于RA：LTC4降至56 - 22%，6 - keto - PGF1α降至43 - 22%，PGE2降至57 - 32%。同样，其代谢物（10⁻⁷、10⁻⁵ M）使OA中释放量降低：LTC4降至99%和60%，PGE2降至42%和20%，6 - keto - PGF1α降至54%和25%。在RA中：LTC4降至81%和45%，PGE2降至61%和30%，6 - keto - PGF1α降至46%和18%。除1组（10⁻⁷ M的LTC4代谢物与泰罗德对照相比）外，所有组均具有显著性（P < 0.05）。总之，在治疗期间关节中预期达到的剂量下，将双重抑制剂替泊沙林及其活性羧酸代谢物与滑膜组织孵育时，可观察到白三烯和前列腺素释放量显著且呈剂量依赖性降低。
