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CN 22-1108/R
Volume 41 Issue 1
Jan.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(1): 92-98

Effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats

DOI: 10.12449/JCH250114
  • 1.

    Graduate School of Hebei Medical University，Shijiazhuang 050017，China

  • 2.

    Department of Pharmacy，Hebei General Hospital，Shijiazhuang 050057，China

  • 3.

    Hebei Key Laboratory of Clinical Pharmacy，Shijiazhuang 050057，China

Research funding:

Natural Science Foundation of Hebei Province (H2022307063)

More Information
  • Corresponding author: DONG Zhanjun， 13313213656@126.com （ORCID： 0000-0001-5349-4907）
  • Received Date: 2024-05-23
  • Accepted Date: 2024-07-05
  • Published Date: 2025-01-25
    Abstract
  •   Objective  To investigate the effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats， and to provide a theoretical basis for drug combination in clinical practice.  Methods  A total of 24 male Sprague-Dawley rats were randomly divided into groups A， B， C， and D， with 6 rats in each group. The rats in groups A and B were given sorafenib control solvent and sorafenib （100 mg/kg）， respectively， by gavage for 7 consecutive days， followed by ertugliflozin （1.5 mg/kg） by gavage on day 7. Blood samples were collected from the angular vein plexus at different time points， and ultra-performance liquid chromatography-tandem mass spectrometry was used to determine the mass concentration of ertugliflozin and plot the plasma concentration-time curves， while the non-compartment model in DAS 2.1.1 software was used to calculate related pharmacokinetic parameters. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.  Results  Compared with group A， group B had significant increases in the AUC0-t and AUC0-∞ of the plasma concentration-time curve of ertugliflozin （both P<0.05）， significant prolongation of t1/2， MRT0-t， and MRT0-∞ （all P<0.05）， and a significant reduction in CLZ/F （P<0.05）. Compared with group C， group D had significant increases in the AUC0-t and AUC0-∞ of ertugliflozin （both P<0.05）， significant prolongation of Tmax， t1/2， MRT0-t， and MRT0-∞ （all P<0.01）， and significant reductions in VZ/F and CLZ/F （both P<0.05）.  Conclusion  Both sorafenib and donafenib can affect the pharmacokinetics of ertugliflozin in rats and significantly increase the plasma exposure of ertugliflozin. The efficacy and adverse drug reactions of ertugliflozin should be closely monitored during combined use in clinical practice and the dose should be adjusted when necessary to avoid the potential risk of drug interaction.

     

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