5-Fluororacil–Induced Gastrointestinal Damage Impairs the Absorption and Anticoagulant Effects of Dabigatran Etexilate

Kazunari Tsujii, Tomoki Hattori, Ayuko Imaoka, Takeshi Akiyoshi, Hisakazu Ohtani

Research output: Contribution to journalArticle

Abstract

Fluoropyrimidines, including 5-fluororacil (5-FU), cause gastrointestinal damage in the clinical setting and might affect the gastrointestinal absorption of concomitantly administered drugs. We aimed to evaluate the effects of fluoropyrimidine-induced gastrointestinal damage on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DABE), an anticoagulant, in rats with gastrointestinal damage induced by the repeated oral administration of 5-FU. Rats were administered DABE orally or dabigatran (DAB), an active moiety of DABE, intravenously. The plasma DAB concentration was determined using liquid chromatography-tandem mass spectrometry. The activated partial thromboplastin time (APTT) was measured before and 30 min after the administration of each drug, and the APTT ratio was calculated. In 5-FU-treated rats, the maximum plasma concentration, the area under the concentration-time curve of DAB after the oral administration of DABE, and the oral bioavailability of DABE were significantly decreased to 18.3%, 22.9%, and 16.3% of the respective control values. The 5-FU-treated rats’ APTT ratio was also significantly lower than the control value. Fluoropyrimidine-induced gastrointestinal damage might reduce the plasma concentration of DAB by impairing DABE absorption and might attenuate the anticoagulant effects of DABE in the clinical setting.

Original languageEnglish
Pages (from-to)1430-1433
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume107
Issue number5
DOIs
Publication statusPublished - 2018 May 1
Externally publishedYes

Fingerprint

Anticoagulants
Partial Thromboplastin Time
Oral Administration
Dabigatran
Tandem Mass Spectrometry
Liquid Chromatography
Pharmaceutical Preparations
Biological Availability
Pharmacokinetics

Keywords

  • bioavailability
  • cancer chemotherapy
  • gastrointestinal
  • intestinal absorption
  • P-glycoprotein
  • pharmacokinetics/pharmacodynamics

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

5-Fluororacil–Induced Gastrointestinal Damage Impairs the Absorption and Anticoagulant Effects of Dabigatran Etexilate. / Tsujii, Kazunari; Hattori, Tomoki; Imaoka, Ayuko; Akiyoshi, Takeshi; Ohtani, Hisakazu.

In: Journal of Pharmaceutical Sciences, Vol. 107, No. 5, 01.05.2018, p. 1430-1433.

Research output: Contribution to journalArticle

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