Miehlke R K, Schneider S, Sörgel F, Muth P, Henschke F, Giersch K H, Münzel P
Department of Arthritis Surgery, North-West Germany Centre of Rheumatology, Sendenhorst.
Drugs. 1990;40 Suppl 5:57-61. doi: 10.2165/00003495-199000405-00014.
The concentration of 6-methoxy-2-naphthylacetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone under steady-state conditions. 6-MNA is the principle metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. Patients suffering from rheumatoid arthritis (n = 12) or osteoarthritis stage III or IV (n = 8) received a daily dose of nabumetone 1 g in the evening starting 4 days prior to surgery. On day 1 an additional loading dose of nabumetone 1 g was given in the morning. At the time of surgery (day 5), blood, synovial tissue and fibrous capsule tissue were taken simultaneously. The samples were analysed by high performance liquid chromatography. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 mg/L, in synovial fluid 34.79 mg/L, in synovial tissue 19.33 mg/g and in fibrous capsule tissue 11.43 mg/g. Under steady-state conditions mean synovial fluid levels of 6-MNA were higher than after administration of a single dose and, in common with levels in synovial tissue, persist in a range sufficient for in vitro cyclo-oxygenase inhibition.
在一项开放性研究中，对20例计划在稳态条件下口服萘丁美酮进行膝关节手术的患者，测定了血浆、滑液、滑膜组织和纤维囊组织中6-甲氧基-2-萘乙酸（6-MNA）的浓度。6-MNA是前体药物萘丁美酮在肝脏中经过广泛首过代谢产生的主要代谢产物。患有类风湿性关节炎（n = 12）或III期或IV期骨关节炎（n = 8）的患者，在手术前4天开始每晚服用1 g萘丁美酮。在第1天上午额外给予1 g萘丁美酮的负荷剂量。在手术时（第5天），同时采集血液、滑膜组织和纤维囊组织。通过高效液相色谱法对样品进行分析。治疗4天后，血浆中6-MNA的平均浓度为40.76 mg/L，滑液中为34.79 mg/L，滑膜组织中为19.33 mg/g，纤维囊组织中为11.43 mg/g。在稳态条件下，6-MNA的平均滑液水平高于单次给药后，并且与滑膜组织中的水平一样，持续在足以抑制体外环氧化酶的范围内。
