Otsuka Noboru, Yataba Ikuko
Senior Specialist Office and Business Planning and Development Division for International Business, Taisho Pharmaceutical Co., Ltd.
Regulatory Affairs, Taisho Pharmaceutical Co., Ltd.
Nihon Yakurigaku Zasshi. 2018;151(5):221-227. doi: 10.1254/fpj.151.221.
Topical non-steroidal anti-inflammatory drugs (NSAIDs) patches are indispensable for the treatment of musculoskeletal diseases, while they are considered less effective than oral NSAIDs. LOQOA tape is a tape-type patch containing esflurbiprofen (SFP) as a major active ingredient with potent cyclooxygenase inhibition and sufficient skin permeability. SFP patch (SFPP) showed higher percutaneous absorption rate, rapid pain relief, and potent anti-inflammatory efficacy comparing with existing NSAIDs patches in rat. SFPP showed dramatically higher synovial fluid and tissue concentration on SFP than that of flurbiprofen (FP) patch after single application to knee osteoarthritis (OA) patients. On the other hand, clinical dosage of SFPP was determined as not more than two patches a day from the estimation of systemic exposure to SFP of SFPP and oral FP. SFPP showed statistically significant differences in pain relief and all the other efficacy end points compared to inactive placebo or FP patch in knee OA patients. Efficacy on OA other than knee joint was also observed. In long-term study of SFPP, using up to two patches a day, a total of 201 patients was included and 161 patients achieved 52-week application. Among drug-related side effects, skin reaction at the application sites was observed in 46.8% and discontinued in 4.3%. Although gastro-intestinal reaction and abnormal changes in laboratory tests related to kidney function were observed as systemic drug-related side effects, most of them were mild in severity. SFPP, the new generation NSAIDs patch, would be one of effective options for the treatment of symptomatic OA patients.
外用非甾体抗炎药（NSAIDs）贴剂是治疗肌肉骨骼疾病不可或缺的药物，但其疗效被认为低于口服NSAIDs。洛索洛芬贴（LOQOA tape）是一种胶带型贴剂，其主要活性成分是依托氟芬（SFP），具有强大的环氧化酶抑制作用和足够的皮肤渗透性。与现有的NSAIDs贴剂相比，SFP贴剂（SFPP）在大鼠中显示出更高的经皮吸收率、更快的疼痛缓解和更强的抗炎功效。在对膝骨关节炎（OA）患者单次应用后，SFPP在滑液和组织中的SFP浓度显著高于氟比洛芬（FP）贴剂。另一方面，根据对SFPP和口服FP的SFP全身暴露量的估计，SFPP的临床用量确定为每天不超过两片。在膝OA患者中，与无活性安慰剂或FP贴剂相比，SFPP在疼痛缓解和所有其他疗效终点方面显示出统计学上的显著差异。在膝关节以外的OA上也观察到了疗效。在SFPP的长期研究中，每天使用两片，共纳入201例患者，161例患者完成了52周的应用。在药物相关的副作用中，46.8%的患者在应用部位出现皮肤反应，4.3%的患者停药。虽然观察到胃肠道反应和与肾功能相关的实验室检查异常变化作为全身性药物相关副作用，但大多数症状较轻。新一代NSAIDs贴剂SFPP将是治疗有症状OA患者的有效选择之一。
