盐酸西那卡塞片在中国健康受试者的药代动力学和生物等效性研究  

Pharmacokinetics and pharmacodynamics studies of cinacalcet hydrochloride tablets in healthy Chinese subjects

作　　者：曹伟[1] 卢志品[1] 熊文刚 伊金玲 程泽能 罗茜 CAO Wei;LU Zhi-pin;XIONG Wen-gang;YI Jin-ling;CHENG Ze-neng;LUO Xi(Department of Scientific Research,First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;Accu BE Pharma Technology lim ited Liability Company,Xiamen 361026,Fujian Province,China;Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,Hunan Province,China)

机构地区：[1]厦门大学附属第一医院科研部,福建厦门361003 [2]莱必宜科技(厦门)有限责任公司,福建厦门361026 [3]中南大学湘雅药学院,湖南长沙410013

出　　处：《中国临床药理学杂志》2020年第6期687-691,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究盐酸西那卡塞片在中国健康受试者中的药代动力学特征,并评价其生物等效性。方法空腹和餐后分别入组32,46例健康受试者,采用随机、开放、两序列、两周期交叉给药的试验设计,受试者单次口服盐酸西那卡塞片受试药物和参比药物25 mg,采用高效液相色谱-串联质谱法测定血浆中西那卡塞浓度,使用PhonenixWinNolin 6.4软件计算药代动力学参数,评价生物等效性。结果单次空腹给药受试药物与参比药物西那卡塞的主要药代动力学参数:Cmax分别(6.10±4.10),(6.06±4.88)ng·mL^-1;tmax分别为(3.45±1.71),(3.60±1.62)h;t1/2分别为(28.00±23.92),(26.39±23.95)h;AUC0-120 h分别为(46.54±37.97),(45.09±39.82)ng·h·mL^-1;AUC0-∞分别为(50.34±41.44),(49.07±44.62)ng·h·mL^-1。单次餐后给药受试药物与参比药物西那卡塞的主要药代动力学参数:Cmax分别(10.80±6.06),(9.84±5.33)ng·mL^-1;tmax分别为(3.35±1.49),(3.35±1.35)h;t1/2分别为(36.24±19.72),(34.61±19.00)h;AUC0-120 h分别为(79.92±42.88),(75.96±39.26)ng·h·mL^-1;AUC0-∞分别为(84.54±45.65),(81.90±41.27)ng·h·mL^-1。两药物的主要药代动力学参数Cmax、AUC0-120 h、AUC0-∞经对数转换后进行方差分析,其90%置信区间空腹状态下分别为92.35%~122.89%,98.30%~119.55%,98.37%~118.77%;餐后状态下分别为98.68%~120.36%,94.93%~106.47%,95.25%~107.01%。结论空腹和餐后状态下,两种盐酸西那卡塞的主要药代动力学参数相近,具有生物等效性。Objective To study the pharmacokinetic characteristics of cinacalcet hydrochloride tablets in healthy Chinese subjects and evaluate its bioequivalence.Methods This was a random,open,two-sequence,two-period,cross design,32 healthy Chinese subjects were enrolled under fasting condition and 46 healthy Chinese subjects were enrolled under fed condition.Each subject received single oral test preparation(T)and reference preparation(R)25 mg.The concentrations of cinacalcet in plasma were determined by LC-MS/MS and calclulated by Phonenix WinNolin 6.4,to evaluate the bioequivablence.Results The main pharmacokinetic parameters of the tested and reference preparations were as follows:the fasting condition Cmax were(6.10±4.10),(6.06±4.88)ng·mL^-1;tmax were(3.45±1.71),(3.60±1.62)h;t1/2 were(28.00±23.92),(26.39±23.95)h;AUC0-120 h were(46.54±37.97),(45.09±39.82)ng·h·m L^-1;AUC0-∞were(50.34±41.44),(49.07±44.62)ng·h·m L^-1.The fed condition Cm ax were(10.80±6.06),(9.84±5.33)ng·m L^-1;tm ax were(3.35±1.49),(3.35±1.35)h;t1/2 were(36.24±19.72),(34.61±19.00)h;AUC0-120 h were(79.92±42.88),(75.96±39.26)ng·h·m L^-1;AUC0-∞were(84.54±45.65),(81.90±41.27)ng·h·m L^-1.The 90%confidence interval of Cm ax,AUC0-120 h and AUC0~8 of test preparation in fasting condition were 92.35%-122.89%,98.30%-119.55%,98.37%-118.77%;in fed condition were98.68%-120.36%,94.93%-106.47%,95.25%-107.01%.Conclusion Both of the two kinds preparatiom of cinacalcet hydrochloride tablets were bioequivalent in fasting condition and fed condition.

关 键 词：盐酸西那卡塞片 中国健康受试者 药代动力学 生物等效性 

分 类 号：R97[医药卫生—药品]