利多卡因凝胶贴膏皮肤外用在健康受试者的生物等效性研究  

Lidocaine gel plaster applied externally to the skin of healthy subjects bioequivalence study

作　　者：王柳[1] 朱刚直[1] 韩胜男 彭辉 童妹 徐朗 康晓飞 赵天勤 何小爱[1] 王红丹 WANG Liu;ZHU Gangzhi;HAN Shengnan;PENG Hui;TONG Mei;XU Lang;KANG Xiaofei;ZHAO Tianqin;HE Xiaoai;WANG Hongdan(PhaseⅠClinical Research Institute,Haikou People's Hospital,Haikou 570208,Hainan Province,China;Hainan Huiyuantang Pharmaceutical Co.,Ltd.,Haikou 570216,Hainan Province,China)

机构地区：[1]海口市人民医院Ⅰ期临床研究室,海南海口570208 [2]海南回元堂药业有限公司,海南海口570216

出　　处：《世界临床药物》2023年第10期1055-1062,共8页World Clinical Drug

摘　　要：目的评价5%利多卡因凝胶贴膏受试制剂与参比制剂在健康受试者皮肤局部外用条件下的生物等效性、皮肤黏附力和刺激性以及安全性。方法采用单中心、随机、开放、单剂量、两周期、两序列、双交叉试验设计,入组的30例健康受试者按照随机表分为RT组和TR组,RT组受试者第1周期贴敷参比制剂,第2周期贴敷受试制剂;TR组受试者第1周期贴敷受试制剂,第2周期贴敷参比制剂,清洗期3 d,每次3贴,连续贴敷12 h。用经方法学验证后的内标法和统计学方法计算主要药代动力学参数,分析两种制剂的生物等效性、黏附力及皮肤刺激性。结果受试制剂与参比制剂血浆峰浓度、0时到最后一个浓度可准确测定的样品采集时间t的血药浓度-时间曲线下面积、0时到无限时间的血药浓度-时间曲线下面积几何均值比的90%置信区间均在80.00%~125.00%;所有受试者所有时点两制剂黏附力完全一致;受试制剂和参比制剂的皮肤刺激性差异无统计学意义(P>0.05)。结论受试制剂与参比制剂具有生物等效性,安全性良好,且受试制剂黏附力非劣效于参比制剂,皮肤刺激性无差异。Objective To evaluate the bioequivalence,skin adhesion,irritation and safety of test preparation and reference preparation of 5%lidocaine gel patch on the skin of healthy volunteers under topical application condition.Methods A single-center,randomized,open-label,single-dose,two-cycle,two-sequence,two-crossover trial was designed.Thirty healthy subjects were randomly divided into RT group and TR group,subjects in RT group were treated with the reference preparation in the first cycle,and test preparation in the second cycle.Subjects in the TR group were treated with the test preparation in the first cycle,and reference preparation in the second cycle.The cleaning period was 3 days,3 patches each time and continuous application for 12 h.The internal standard method and statistical method were used to calculate the main pharmacokinetic parameters,and the bioequivalence,adhesion and skin irritation of the two formulations were analyzed.Results The 90%confidence interval for the geometric mean ratio of plasma peak concentration of the test preparation and the reference preparation,the area under the blood concentration-time curve from 0 to the time t that can be accurately measured,and the area under the blood concentration-time curve from 0 to infinite time were all 80.00%to 125.00%.The adhesive force of the two formulations were completely consistent among all subjects at all time points.There was no statistically significant difference in skin irritation between the test preparation and the reference preparation(P>0.05).Conclusion The test preparation was bioequivalent to the reference preparation,with good safety,and the test preparation was not inferior to the reference preparation in adhesive force,and there was no difference in skin irritation.

关 键 词：利多卡因 生物等效性 药代动力学 黏附力 皮肤刺激性 

分 类 号：R979.1[医药卫生—药品]