目的:在临床前研究中,依托度酸,一种非甾体抗炎药,影响瞬时受体电位锚蛋白1(TRPA1)激活。然而,依托度酸和TRPA1之间的体外相互作用是否在人体内转化为TRPA1功能的改变仍有待研究。
方法:随机,双盲,进行了塞来昔布对照研究,以评估依托度酸对TRPA1介导的皮肤血流量(DBF)变化的影响15健康,男性志愿者年龄在18至45岁之间。超过四次研究访问,分开至少五天的清洗,口服单次或4倍剂量的依托度酸200mg或塞来昔布200mg.给药后两小时,通过评估肉桂醛诱导的DBF变化来评估TRPA1功能性。在肉桂醛施用后60分钟内,使用激光多普勒成像对DBF变化进行定量并以灌注单位(PU)表示。计算相应的曲线下面积(AUC0-60min)作为汇总测量。使用线性混合模型与事后Dunnett进行统计分析。
结果:与未治疗相比,单剂量依托度酸和塞来昔布均未抑制肉桂醛诱导的DBF变化(AUC0-60min±SEM为17,751±1,514PU*min和17,532±1,706PU*minvs.19,274±1,031个PU*最小,分别,两者p=1.00)。同样,两种化合物的四倍剂量也未能抑制肉桂醛诱导的DBF变化(19,235±1,260PU*min和19,367±1,085PU*minvs.19,274±1,031个PU*最小,分别,两者p=1.00)。
结论:依托度酸不影响肉桂醛诱导的DBF变化,这表明它不会改变TRPA1在人体内的功能。
OBJECTIVE: In preclinical research,
etodolac, a non-steroidal anti-inflammatory drug, affected transient receptor potential ankyrin 1 (TRPA1) activation. Yet, whether the in vitro interaction between
etodolac and TRPA1 translates to altered TRPA1 functionality in vivo in human remains to be investigated.
METHODS: A randomized, double-blinded, celecoxib-controlled study was conducted to assess the effect of
etodolac on TRPA1-mediated dermal blood flow (DBF) changes on the forearm of 15 healthy, male volunteers aged between 18 and 45 years. Over four study visits, separated by at least five days wash-out, a single or four-fold dose of
etodolac 200 mg or celecoxib 200 mg was administered orally. Two hours post-dose, TRPA1 functionality was evaluated by assessing cinnamaldehyde-induced DBF changes. DBF changes were quantified and expressed in Perfusion Units (PUs) using laser Doppler imaging during 60 min post-cinnamaldehyde application. The corresponding area under the curve (AUC0-60min) was calculated as summary measure. Statistical analysis was performed using Linear mixed models with post-hoc Dunnett.
RESULTS: Neither the single dose of etodolac nor celecoxib inhibited the cinnamaldehyde-induced DBF changes compared to no treatment (AUC0-60min ± SEM of 17,751 ± 1,514 PUs*min and 17,532 ± 1,706 PUs*min vs. 19,274 ± 1,031 PUs*min, respectively, both p=1.00). Similarly, also a four-fold dose of both compounds failed to inhibit the cinnamaldehyde-induced DBF changes (19,235 ± 1,260 PUs*min and 19,367 ± 1,085 PUs*min vs. 19,274 ± 1,031 PUs*min, respectively, both p=1.00).
CONCLUSIONS: Etodolac did not affect the cinnamaldehyde-induced DBF changes, suggesting that it does not alter TRPA1 functionality in vivo in human.