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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (2): 171-177.doi: 10.12092/j.issn.1009-2501.2023.02.007

• 临床药理学 • 上一篇    下一篇

盐酸西那卡塞片在中国健康人群的生物等效性研究

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1,2,范晓1,2,刘赛4,熊守军4,方平飞1,2   

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

  • 收稿日期:2022-04-11 修回日期:2023-02-08 出版日期:2023-02-26 发布日期:2023-03-10
  • 通讯作者: 方平飞,男,博士,副主任药师,硕士生导师,研究方向:体内药物相互作用研究与药代动力学研究。 E-mail:fangpingfei@csu.edu.cn
  • 作者简介:燕强勇,男,硕士,主管药师,研究方向:药物临床研究与药代动力学研究。 E-mail:yanqiangyong@csu.edu.cn

Bioequivalence study of cinacalcet hydrochloride tablets in healthy Chinese volunteers

YAN Qiangyong1,2, XIANG Daxiong1,2, ZHU Ronghua1,2, YANG Lingfeng2,3, YANG Xiding1,2, LI Jingjing1,2, FAN Xiao1,2, LIU Sai4, XIONG Shoujun4, FANG Pingfei1,2   

  1. 1Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; 2Phase I Clinical Trial Center, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; 3Department of Metabolism & Endocrinology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; 4Nanjing Hencer Pharmaceutical Co., Ltd., Nanjing 211200, Jiangsu, China
  • Received:2022-04-11 Revised:2023-02-08 Online:2023-02-26 Published:2023-03-10

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Cmax分别为(5.96±4.15)、(6.11±4.08)ng/mL,AUC0-72h分别为(45.82±30.20)、(46.11±29.50) ng·h·mL-1,AUC0-∞分别为(49.65±33.64)、(49.63±32.01)ng·h·mL-1,Tmax分比为4.5[1.0,6.0]和4.5[1.0,6.0] h,t1/2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Cmax分别为(11.14±5.24)、(10.24±5.39)ng/mL,AUC0-72h分别为(76.70±39.34)、(75.18±34.36) ng·h·mL-1,AUC0-∞分别为(83.28±43.00)、(81.38±38.03) ng·h·mL-1,Tmax分比为3.0[1.5,5.0]和4.3[1.5,7.0] h,t1/2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AUC0-72h、AUC0-∞、Cmax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。

关键词: 西那卡塞, 生物等效性, 液相色谱-串联质谱法, 药动学

Abstract:

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: Cmax (5.96±4.15) and (6.11±4.08) ng/mL, AUC0-72h (45.82±30.20) and (46.11±29.50) ng·h·mL-1, AUC0-∞  (49.65±33.64) and (49.63±32.01) ng·h·mL-1, Tmax (4.5[1.0, 6.0]) and (4.5[1.0, 6.0]) h, t1/2 (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: Cmax (11.14±5.24) and  (10.24±5.39) ng/mL, AUC0-72h (76.70±39.34) and (75.18±34.36) ng·h·mL-1, AUC0-∞ (83.28±43.00) and (81.38±38.03) ng·h·mL-1, Tmax (3.0[1.5,5.0]) and (4.3[1.5,7.0]) h, t1/2 (28.07±6.37) and (27.46±5.44) h, respectively. The 90%confidence intervals of the geometric average ratios of Cmax, AUC0-72h and AUC0-∞ were all within the equivalent interval of 80.00%-125.00%. CONCLUSION: Two formulations of cinacalcet tablets are bioequivalent and safe.

Key words: cinacalcet, bioequivalence, LC-MS/MS, pharmacokinetics

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