普瑞巴林胶囊在中国健康受试者空腹和餐后状态下的生物等效性研究  

Bioequivalence study of pregabalin capsule in Chinese healthy adults

作　　者：张吉刚[1] 查怡鑫 金舒静 徐梅 张铭健 薛雯元 张姝月 董志奎 文静 丁雪鹰 ZHANG Ji-gang;ZHA Yi-xin;JIN Shu-jing;XU Mei;ZHANG Ming-jian;XUE Wen-yuan;ZHANG Shu-yue;DONG Zhi-kui;WEN Jing;DING Xue-ying(Phase I Clinical Research Center,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200080,China;Nanjing Hailing Traditional Chinese Medicine Pharmaceutical Art Technical Research Co.,Ltd,Nanjing 210000,China;Yangtze River Pharmaceutical Group Beijing Haisha Consulting Co.,Ltd,100044,China)

机构地区：[1]上海交通大学医学院附属第一人民医院Ⅰ期临床试验研究室,上海200080 [2]南京海陵中药制药工艺技术研究有限公司,江苏南京210000 [3]北京海莎咨询有限公司,北京100044

出　　处：《中国临床药理学杂志》2023年第21期3159-3163,共5页The Chinese Journal of Clinical Pharmacology

基　　金：上海松江区卫生健康委员会松江区科技攻关基金资助项目(2020SJ299)。

摘　　要：目的研究普瑞巴林胶囊仿制药与原研药在中国健康受试者中单剂量空腹和餐后条件下给药的生物等效性。方法用随机、开放、两制剂、单次给药、两序列、双交叉设计,共纳入48例(空腹试验24例,餐后试验24例)成年男性和女性受试者随机交叉给药。分别单次口服受试制剂和参比制剂125 mg,用液相色谱-串联质谱(LC-MS/MS)法测定血浆中普瑞巴林的浓度。用SAS 9.3软件计算药代动力学参数,并进行生物等效性分析。结果空腹组的普瑞巴林胶囊受试制剂和参比制剂主要药代动力学参数如下:AUC_(0-t)分别为(30962.30±5474.72)和(31236.29±4571.08)ng·mL^(-1)·h,AUC_(0-∞)分别为(31323.18±5557.42)和(31603.88±4634.23)ng·mL^(-1)·h,C_(max)分别为(4967.92±898.10)和(5190.83±1078.93)ng·mL^(-1),T_(max)分别为1.00 h和0.88 h,t_(1/2)分别为(5.43±0.57)和(5.47±0.57)h。餐后组的普瑞巴林胶囊受试制剂和参比制剂主要药代动力学参数如下:AUC_(0-t)分别为(28440.85±2881.43)和(28736.69±3043.43)ng·mL^(-1)·h,AUC_(0-∞)分别为(28742.84±2880.59)和(29024.50±3057.91)ng·mL^(-1)·h,C_(max)分别为(3159.58±446.93)和(3165.83±426.90)ng·mL^(-1),T_(max)分别为3.50 h和4.25 h,t_(1/2)分别为(5.10±0.57)和(5.07±0.60)h。在空腹及餐后条件下,受试制剂与参比制剂主要药代动力学参数的90%置信区间均在80.00%~125.00%。结论在空腹及餐后条件下,中国健康成年受试者单次口服普瑞巴林胶囊仿制药与原研药具有生物等效性。Objective To compare the bioequivalence of the domestic and imported pregabalin capsule in Chinese healthy adults under single dose fasting and fed conditions.Methods This randomized,open-label,two drugs,single-dose,single-center,two-period cross over study assigned 48 healthy adults to receive a single 125 mg dose of pregabalin capsule(either domestic or imported capsule at one single period)under fasting(n=24 cases)or fed(n=24 cases)conditions.The drug was orally administrated.The plasma concentrations of the drug were quantified by LC-MS/MS method.The pharmacokinetic parameters were calculated by SAS 9.3 software and bioequivalence analysis was performed.Results Under fasting condition,the main pharmacokinetic parameters of pregabalin capsule were as follows:AUC0-t were(30962.30±5474.72)and(31236.29±4571.08)ng·mL^(-1)·h,AUC_(0-∞)were(31323.18±5557.42)and(31603.88±4634.23)ng·mL^(-1)·h,C_(max) were(4967.92±898.10)and(5190.83±1078.93)ng·mL^(-1),t_(max) were 1.00 and 0.88 h,t1/2 were(5.43±0.57)and(5.47±0.57)h.Under fed condition,the main pharmacokinetic parameters of pregabalin capsule were as follows:AUC_(0-t)were(28440.85±2881.43)and(28736.69±3043.43)ng·mL^(-1)·h,AUC0-∞were(28742.84±2880.59)and(29024.50±3057.91)ng·mL^(-1)·h,C_(max) were(3159.58±446.93)and(3165.83±426.90)ng·mL^(-1),T_(max) were 3.50 h and 4.25 h,t_(1/2) were(5.10±0.57)and(5.07±0.60)h.Under fasting and fed conditions,the 90%confidence intervals of the main pharmacokinetic parameters of the test and the reference drugs were 80.00%-125.00%,which met the criteria for bioequivalence evaluation.Conclusion Under both fasting and fed conditions,the domestic and imported pregabalin capsule were bioequivalent in Chinese healthy adults.

关 键 词：普瑞巴林胶囊 生物等效性 血浆 药代动力学 液相色谱-串联质谱 

分 类 号：R97[医药卫生—药品]