枸橼酸托法替布片在健康中国受试者体内的生物等效性研究  

Bioequivalence study of tofacitinib citrate tablets in Chinese healthy subjects

作　　者：李晓斌[1] 喻明[1] 汪楠[1] 胡妮娜 王宁[1] 倪钰锋 陈昱竹 王诗婷 高雪 王文萍[1] LI Xiao-bin;YU Ming;WANG Nan;HU Ni-na;WANG Ning;NI Yu-feng;CHEN Yu-zhu;WANG Shi-ting;GAO Xue;WANG Wen-ping(Phase I Clinical Trial Ward,National Drug Clinical Institution,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Yangtze River Pharmaceutical Group Co.,Ltd.,Taizhou 225300,Jiangsu Province,China)

机构地区：[1]辽宁中医药大学附属医院国家药物临床试验机构Ⅰ期临床病房,辽宁沈阳110032 [2]扬子江药业集团有限公司,江苏泰州225300

出　　处：《中国临床药理学杂志》2022年第2期161-165,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划项目基金资助项目(2018YFC1311600);辽宁省自然科学基金资助项目(20170520022);辽宁省“兴辽英才计划”基金资助项目(XLYC1802008);辽宁省中药临床药物代谢动力学重点实验室基金资助项目(辽科发2005-16);辽宁中医药大学中药临床药理学科建设基金资助项目(辽中医校发2016-198)。

摘　　要：目的评价2种枸橼酸托法替布片在中国健康受试者中的生物等效性和安全性。方法按单次给药、随机、开放、两周期、双交叉试验设计。空腹、餐后条件下各入组30例受试者,随机交叉单次口服枸橼酸托法替布受试制剂和参比制剂各5 mg,用HPLC-MS/MS法检测血浆中托法替布的浓度,用Phoenix Win Nonlin 7.0软件计算药代动力学参数,并进行2种制剂的生物等效性评价。结果受试者服用受试制剂和参比制剂后,空腹组血浆中枸橼酸托法替布的主要药代动力学参数如下:C_(max)分别为(69.02±21.25)和(66.64±17.48)ng·mL^(-1),AUC_(0-t)分别为(167.69±47.42)和(167.34±45.92)ng·mL^(-1)·h,AUC_(0-∞)分别为(168.75±47.50)和(168.40±46.26)ng·mL^(-1)·h。餐后组血浆中枸橼酸托法替布主要药代动力学参数如下:受试制剂和参比制剂的C_(max)分别为(50.51±18.01)和(50.81±15.98)ng·mL^(-1),AUC_(0-t)分别为(180.60±38.12)和(182.83±41.53)ng·mL^(-1)·h,AUC_(0-∞)分别为(181.83±38.29)和(183.85±41.82)ng·mL^(-1)·h。2种制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)经对数转换后90%可信区间分别为空腹状态下92.21%~112.86%,97.15%~105.29%和97.18%~105.25%;餐后状态下84.52%~114.92%,96.43%~102.58%和96.60%~102.74%。结论2种枸橼酸托法替布片在中国健康受试者中具有生物等效性,安全性良好。Objective To evaluate the bioequivalence of two kinds of tofacitinib citrate tablets in healthy Chinese subjects.Methods This was a single-center,randomized,open-lable,single-dose,two-period,two-way crossover pharmacokinetic study.A total of 30 subjects respectively for fasting and fed state were given a single oral dose of test and reference preparation of tofacitinib citrate tablet(each 5 mg).Plasma concentration of tofacitinib was measured by HPLC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 7.0 software.Results The main pharmacokinetic parameters of tofacitinib of test and reference preparations were as follows:under fasting state C_(max) were(69.02±21.25)and(66.64±17.48)ng·mL^(-1),AUC_(0-t) were(167.69±47.42)and(167.34±45.92)ng·mL^(-1)·h,AUC_(0-∞)were(168.75±47.50)and(168.40±46.26)ng·mL^(-1)·h.Under fed state C_(max) were(50.51±18.01)and(50.81±15.98)ng·mL^(-1),AUC_(0-t) were(180.60±38.12)and(182.83±41.53)ng·mL^(-1)·h,AUC_(0-∞)were(181.83±38.29)and(183.85±41.82)ng·mL^(-1)·h.The 90%CIs for C_(max),AUC_(0-t) and AUC_(0-∞)of test formulation in the fasting state were 92.21%-112.86%,97.15%-105.29%and 97.18%-105.25%;in the fed state were 84.52%-114.92%,96.43%-102.58%and 96.60%-102.74%.Conclusion The test formulation and reference formulation of tofacitinib citrate tablets are determined to be bioequivalent.

关 键 词：枸橼酸托法替布片 中国健康受试者 生物等效性 

分 类 号：R97[医药卫生—药品]