盐酸西那卡塞片在中国健康人群的生物等效性研究  

Bioequivalence study of cinacalcet hydrochloride tablets in healthy Chinese volunteers

作　　者：燕强勇[1,2] 向大雄[1,2] 朱荣华[1,2] 杨玲凤[2,3] 阳喜定[1,2] 李晶晶 范晓[1,2] 刘赛 熊守军 方平飞[1,2] YAN Qiangyong;XIANG Daxiong;ZHU Ronghua;YANG Lingfeng;YANG Xiding;LI Jingjing;FAN Xiao;LIU Sai;XIONG Shoujun;FANG Pingfei(Department of Pharmacy,the Second Xiangya Hospital,Central South University,Changsha 410011,Hunan,China;Phase I Clinical Trial Center,the Second Xiangya Hospital,Central South University,Changsha 410011,Hunan,China;Department of Metabolism&Endocrinology,the Second Xiangya Hospital,Central South University,Changsha 410011,Hunan,China;Nanjing Hencer Pharmaceutical Co.,Ltd.,Nanjing 211200,Jiangsu,China)

机构地区：[1]中南大学湘雅二医院药学部,湖南长沙410011 [2]中南大学湘雅二医院药物Ⅰ期临床研究室,湖南长沙410011 [3]中南大学湘雅二医院代谢内分泌科,湖南长沙410011 [4]南京恒生制药有限公司,江苏南京211200

出　　处：《中国临床药理学与治疗学》2023年第2期171-177,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:评价国产盐酸西那卡塞片与进口原研盐酸西那卡塞片在中国健康人群的生物等效性。方法:采用随机、开放、两周期交叉试验设计,48名健康受试者分别在空腹和餐后条件下单次口服盐酸西那卡塞片受试制剂和参比制剂。采用经验证的液相色谱-串联质谱法测定血浆中西那卡塞的浓度,应用Phoenix WinNonlin 8.0进行药动学参数计算和统计分析。结果:空腹试验中受试制剂和参比制剂的主要药动学参数C_(max)分别为(5.96±4.15)、(6.11±4.08)ng/mL,AUC_(0-72h)分别为(45.82±30.20)、(46.11±29.50)ng·h·mL^(-1),AUC_(0-∞)分别为(49.65±33.64)、(49.63±32.01)ng·h·mL^(-1),T_(max)分比为4.5[1.0,6.0]和4.5[1.0,6.0]h,t_(1/2)分别为(23.15±9.23)和(22.43±8.81)h。餐后试验中受试制剂和参比制剂的主要药动学参数C_(max)分别为(11.14±5.24)、(10.24±5.39)ng/mL,AUC_(0-72h)分别为(76.70±39.34)、(75.18±34.36)ng·h·mL^(-1),AUC_(0-∞)分别为(83.28±43.00)、(81.38±38.03)ng·h·mL^(-1),T_(max)分比为3.0[1.5,5.0]和4.3[1.5,7.0]h,t_(1/2)分别为(28.07±6.37)和(27.46±5.44)h。受试制剂与参比制剂空腹和餐后条件下的AUC_(0-72h)、AUC_(0-∞)、C_(max)几何均值比值的90%置信区间落在80.00%~125.00%的范围内。结论:两种制剂在空腹和餐后给药的条件下均生物等效,安全性良好。AIM:To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers.METHODS:A randomized,open,double-period and crossover trial was conducted,48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition.The concentration of cinacalcet was determined by validated LC-MS/MS method.Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence.RESULTS:The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows:C_(max)(5.96±4.15)and(6.11±4.08)ng/mL,AUC_(0-72h)(45.82±30.20)and(46.11±29.50)ng·h·mL^(-1),AUC_(0-∞)(49.65±33.64)and(49.63±32.01)ng·h·mL^(-1),T_(max)(4.5[1.0,6.0])and(4.5[1.0,6.0])h,t_(1/2)(23.15±9.23)and(22.43±8.81)h,respectively.Under fed condition,the main pharmacokinetic parameters of test tablets and reference tablets were as follows:C_(max)(11.14±5.24)and(10.24±5.39)ng/mL,AUC_(0-72h)(76.70±39.34)and(75.18±34.36)ng·h·mL^(-1),AUC_(0-∞)(83.28±43.00)and(81.38±38.03)ng·h·mL^(-1),T_(max)(3.0[1.5,5.0])and(4.3[1.5,7.0])h,t_(1/2)(28.07±6.37)and(27.46±5.44)h,respectively.The 90%confidence intervals of the geometric average ratios of C_(max),AUC_(0-72h)and AUC_(0-∞)were all within the equivalent interval of 80.00%-125.00%.CONCLUSION:Two formulations of cinacalcet tablets are bioequivalent and safe.

关 键 词：西那卡塞 生物等效性 液相色谱-串联质谱法 药动学 

分 类 号：R969.1[医药卫生—药理学]