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中国临床药理学与治疗学 ›› 2024, Vol. 29 ›› Issue (11): 1295-1299.doi: 10.12092/j.issn.1009-2501.2024.11.012

• 临床药理学 • 上一篇    下一篇

利伐沙班片在中国健康受试者中的药动学及生物等效性评价

解染1,2,程璐1,2,周双1,张雪媛3,王晓如4,赵侠1,2,何旭1,5,6,赵  楠1,2,贾博1,2,崔一民1,6
  

  1. 1北京大学第一医院药学部,2北京大学第一医院药物临床试验机构,北京100034;3上海海翊石医药科技有限公司,上海 201318;4石药集团中奇制药技术(石家庄)有限公司,石家庄 050000,河北;5北京大学第一医院临床药理研究所,北京100034;6北京大学药学院药事管理与临床药学系,  北京 100191

  • 收稿日期:2023-11-15 修回日期:2024-02-20 出版日期:2024-11-26 发布日期:2024-10-24
  • 通讯作者: 崔一民,男,博士,教授,博士生导师,主任药师,研究方向:药物临床试验管理及临床药学。 E-mail: cui.pharm@pkufh.com
  • 作者简介:解染,女,硕士,主管药师,研究方向:药物临床试验管理。 E-mail: xieran0000@163.com
  • 基金资助:
    国家科技重大专项—重大新药创制课题资助项目(2017ZX09101001)

Pharmacokinetics and bioequivalence of rivaroxaban tablet in Chinese healthy subjects 

XIE Ran1,2, CHENG Lu1,2, ZHOU Shuang1, ZHANG Xueyuan3, WANG Xiaoru4, ZHAO Xia1,2, HE Xu1,5,6, ZHAO Nan1,2, JIA Bo1,2, CUI Yimin1,6   

  1. 1Department of Pharmacy, 2Drug Clinical Trial institution,Peking University First Hospital, Beijing 100034, China; 3Shanghai Innovstone Therapeutics Limited, Shanghai 201318, China; 4CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Shijiazhuang 050000, Hebei, China; 5Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China; 6Administration and Clinical Pharmacy School of Pharmaceutical Science, Department of Pharmacy, Peking University, Beijing 100191, China
  • Received:2023-11-15 Revised:2024-02-20 Online:2024-11-26 Published:2024-10-24

摘要:

目的:评价利伐沙班片在人体中的生物等效性。方法:空腹和餐后组各入选28例健康受试者,试验采用四周期、完全重复交叉设计,各周期服药剂量为10 mg(受试制剂T或参比制剂R)。采用HPLC-MS /MS测定血样中利伐沙班的浓度。采用Phoenix WinNonlin 7.0 软件计算相关药代动力学(PK)参数,进而评价两制剂是否等效。结果:空腹组T和R两制剂的Cmax分别为(186.57±56.41)、(187.61±50.89) ng/mL;AUC0-t分别为(1 156.21±335.85)、(1 177.59±343.72) h·ng·mL-1;AUC0-∞分别为(1 235.77±384.03)、(1 223.53±392.10) h·ng·mL-1。两制剂的上述三个PK参数几何均值比(GMR)的90%置信区间(CI)分别为90.81%~105.67%,92.83%~103.85%,95.04%~107.13%;个体内变异比率90%CI上限值分别为1.56、1.41、1.73。餐后组T和R两制剂的Cmax分别为(207.81±45.26)、(211.04±36.62)ng/mL;AUC0-t分别为(1 271.26±260.92)、(1 233.23±201.85)h·ng·mL-1;AUC0-∞分别为(1 290.76±264.90)、(1 251.68±203.73)ng·h·mL-1。两制剂的上述三个PK参数GMR 90%CI分别为92.82%~102.28%,97.68%~106.68%,97.71%~106.68%;个体内变异比率90%CI上限值分别为1.76、1.47、1.47。结论:两种利伐沙班片在人体内生物等效。

关键词: 利伐沙班, 生物等效性, 窄治疗窗药物

Abstract:

AIM: To evaluate the bioequivalence of the two rivaroxaban tablets in Chinese healthy subjects. METHODS: Twenty-eight subjects under fasting status and twenty-eight subjects under fed status were enrolled in the study. This study was designed as a four period, fully repetitive, crossover study. All subjects were administered test (T) and reference (R) rivaroxaban tablets (10 mg) under fasting and fed condition respectively. Liquid chromatography - tandem mass spectrometry was used to detect the concentrations of rivaroxaban in plasma. WinNonlin 7.0 was used to calculate the main pharmacokinetic parameters (PK) and to evaluate the bioequivalence. RESULTS: In fasting group, the main pharmacokinetic parameters of T and R preparation were as follows: Cmax were(186.57±56.41) and (187.61±50.89) ng/mL; AUC0-t were (1 156.21±335.85) and (1 177.59±343.72) h·ng·mL-1; AUC0-∞ were (1 235.77±384.03) and (1 223.53±392.10) ng·h·mL-1. The 90% confidential interval (CI) of the three main parameters were 90.81%-105.67%, 92.83%-103.85% and 95.04%-107.13%. The upper limit of the 90% CI for the test- to- reference ratio of the within-subject of Cmax, AUC0-t  and  AUC0-∞ were 1.56, 1.41 and 1.73. In fed group, the main pharmacokinetic parameters of T and R preparation were as follows: Cmax were (207.81±45.26) and (211.04±36.62) ng/mL; AUC0-t were (1 271.26±260.92) and (1 233.23±201.85) h·ng·mL-1; AUC0-∞ were (1 290.76±264.90) and (1 251.68±203.73) ng·h·mL-1. The 90% CI of the three main parameters were 92.82%-102.28%, 97.68%-106.68% and 97.71%-106.68%. The upper limit of the 90% CI for the test- to- reference ratio of the within-subject of Cmax, AUC0-t and AUC0-∞ were 1.76, 1.47 and 1.47. CONCLUSION:The two preparations of rivaroxaban tablets were bioequivalent.

Key words: rivaroxaban, bioequivalence, narrow-window drugs

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