氯巴占片在中国健康成年受试者中的生物等效性研究  

Bioequivalence Study of Clobazam Tablet in Chinese Healthy Subjects

作　　者：张学农[1] 王燕燕[1] 李莉娥 张敏 宋俐萍 易梦娟 吴先迪 游辉[1] ZHANG Xuenong;WANG Yanyan;LI Lie;ZHANG Min;SONG Liping;YI Mengjuan;WU Xiandi;YOU Hui(Department of Pharmacy,Yichang Central People's Hospital·the First College of Clinical Medical Science,China Three Gorges University,Yichang 443003,China;Yichang Humanwell Pharmaceutical Co.,LTD.,Yichang 443003,China)

机构地区：[1]三峡大学第一临床医学院·宜昌市中心人民医院药学部,宜昌443003 [2]宜昌人福药业有限责任公司,宜昌443003

出　　处：《医药导报》2023年第12期1785-1790,共6页Herald of Medicine

摘　　要：目的研究氯巴占片在中国健康受试者体内的药代动力学特征,并评价受试者空腹或餐后状态下口服受试制剂T和参比制剂R的生物等效性。方法采用随机、开放、单剂量、两周期、两序列、双交叉生物等效性试验设计,空腹研究和餐后研究拟分别入组34例和30例受试者。受试者每周期单次口服20 mg氯巴占T或R,清洗期28 d。采用液相色谱串联质谱方法(LC-MS/MS)检测血浆中氯巴占及其活性代谢产物N-去甲基氯巴占的浓度,非房室模型计算二者的药动学参数。根据氯巴占主要药动学参数几何均值比的90%置信区间(CI)评价受试制剂和参比制剂是否生物等效性。结果空腹研究,受试制剂和参比制剂氯巴占峰浓度(C_(max))、AUC_(0-t)和AUC_(0-∞)几何均值比的90%CI分别是94.46%~103.82%、99.64%~103.62%、99.39%~103.51%。餐后研究,受试制剂和参比制剂氯巴占C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比的90%CI分别是93.86%~106.02%、100.37%~104.51%、100.71%~104.63%。结论受试制剂和参比制剂氯巴占的C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比的90%CI均在80.00%~125.00%,两种制剂具有生物等效性。Objective To study the pharmacokinetic characteristics of clobazam tablet in Chinese healthy subjects and evaluate the bioequivalence of test preparation(T)and reference preparation(R)under fasting or fed conditions.Methods A randomized,open-label,single-dose,two-period,two-way crossover bioequivalence trial was performed.34 healthy subjects were enrolled in fasting study and 30 in fed study.Each subjects received a single dose of T 20 mg or R 20 mg with a washout period of 28 days.Plasma concentrations of clobazam and its active metabolite,N-desmethylclobazam were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters of clobazam and N-desmethylclobazam were calculated by non-compartment model.Geometric mean values for the T/R ratios of clobazam's main pharmacokinetic parameters and their corresponding 90 percent confidence intervals(CI)were evaluated to assess bioequivalence of the two preparations.Results In fasting study,the 90 percent CI of the geometric mean values for the T/R ratios were 94.46 to 103.82 percent for C_(max),99.64 to 103.62 percent for AUC_(0-t)and 99.39 to 103.51 percent for AUC_(0-∞),respectively.In fed study,the 90 percent CI of the geometric mean values for the T/R ratios of were 93.86 to 106.02 percent for C_(max),100.37 to 104.51 percent for AUC_(0-t)and 100.71 to 104.63 percent for AUC_(0-∞),respectively.Conclusion In this study,the 90 percent CI of the geometric mean values of C_(max),AUC_(0-t)and AUC_(0-∞)for T/R ratios were all within the acceptable bioequivalence limits of 80 to 125 percent for clobazam.Therefore two formulations were considered bioequivalent.

关 键 词：氯巴占 药动学 生物等效性 

分 类 号：R973.3[医药卫生—药品]