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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2024, Vol. 29 ›› Issue (11): 1295-1299.doi: 10.12092/j.issn.1009-2501.2024.11.012

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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

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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