Efe Turgay, Sagnak Ercan, Roessler Philip P, Getgood Alan, Patzer Thilo, Fuchs-Winkelmann Susanne, Peterlein Christian D, Schofer Markus D
Department of Orthopaedics and Rheumatology, University Hospital Marburg, Baldingerstrasse, 35043, Marburg, Germany,
Knee Surg Sports Traumatol Arthrosc. 2014 Feb;22(2):345-50. doi: 10.1007/s00167-013-2408-0. Epub 2013 Jan 22.
The present study was designed to evaluate the penetration of diclofenac sodium 4 % spray gel in synovial tissue, synovial fluid and blood plasma after topical application in subjects with joint effusions and planned total knee arthroplasty (TKA) due to osteoarthritis.
A total of 39 patients were randomised to two- or three-times daily application of diclofenac sodium 4 % spray gel to knees requiring surgery over a treatment period of 3 days. Within 8 h after the last application, TKA was conducted, and the diclofenac concentrations in synovial tissue, synovial fluid and blood plasma were measured by liquid chromatography.
The median diclofenac concentration was approximately 10-20-fold higher in synovial tissue (36.2 and 42.8 ng/g) than in synovial fluid (2.6 and 2.8 ng/mL) or plasma (3.9 and 4.1 ng/mL) in both treatment groups. Dose proportionality for any compartment or treatment groups could not be detected. Treatment-related adverse events were noted in two cases and limited to skin reactions.
Diclofenac sodium 4 % spray gel was found to penetrate the skin locally in substantial amounts and thus reach the desired target tissue. Concentrations were not dose-dependent, and application was well tolerated by 97.4 % of patients. Topical application of diclofenac should be considered a valuable alternative to systemic NSAID therapy in the initial treatment of osteoarthritis.
本研究旨在评估4%双氯芬酸钠喷雾凝胶在因骨关节炎导致关节积液并计划进行全膝关节置换术（TKA）的受试者局部应用后，在滑膜组织、滑液和血浆中的渗透情况。
总共39例患者被随机分为两组，在3天的治疗期内，每天两次或三次将4%双氯芬酸钠喷雾凝胶应用于需要手术的膝盖。在最后一次应用后8小时内进行TKA手术，并通过液相色谱法测量滑膜组织、滑液和血浆中的双氯芬酸浓度。
在两个治疗组中，滑膜组织中的双氯芬酸浓度中位数（36.2和42.8 ng/g）比滑液（2.6和2.8 ng/mL）或血浆（3.9和4.1 ng/mL）中大约高10至20倍。未检测到任何隔室或治疗组的剂量比例关系。有两例出现与治疗相关的不良事件，且仅限于皮肤反应。
发现4%双氯芬酸钠喷雾凝胶能大量局部穿透皮肤，从而到达预期的靶组织。浓度不依赖于剂量，97.4%的患者对该应用耐受性良好。在骨关节炎的初始治疗中，双氯芬酸的局部应用应被视为全身非甾体抗炎药治疗的一种有价值替代方法。
