Drug delivery of oral anti-cancer fluoropyrimidine agents

Koh Miura, Hiroshi Shima, Naoko Takebe, Julie Rhie, Kennichi Satoh, Yoichiro Kakugawa, Masayuki Satoh, Makoto Kinouchi, Kuniharu Yamamoto, Yasuhiro Hasegawa, Masaaki Kawai, Kousuke Kanazawa, Tsuneaki Fujiya, Michiaki Unno, Ryuichi Katakura

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)


Introduction: Sixty years since its introduction, 5-FU still forms the core of chemotherapy regimens for many types of malignancies. 5-FU is a time-dependent drug but is rapidly degraded in plasma by dihydropyrimidine dehydrogenase (DPD). Although originally developed in an intravenous form, 5-FU oral prodrugs were developed with the goal of improving efficacy and minimizing toxicity as well as to capitalize on the advantages of oral drug administration. The inactive 5-FU prodrug is gradually converted into the active form in the systemic circulation. UFT, S-1, and capecitabine are oral 5-FU prodrugs currently in clinical use. However, the efficacy of 5-FU can be further improved by its combination with DPD inhibitors and biochemical modulators, such as uracil and leucovorin, in addition to modifying administration schedules. Areas covered: We focused on the drug delivery of oral 5-FU prodrugs, their pharmacokinetics, and the development of DPD inhibitors. Since oral 5-FU prodrugs have been formulated into combination drugs, we also discussed the regulatory approval of combination drugs. Expert opinion: Many regimens that include intravenously administered 5-FU can be replaced by oral 5-FU prodrugs. Patients would benefit from development of combination 5-FU oral prodrug formulations and its associated path through the combination drug regulatory approval process.

Original languageEnglish
Pages (from-to)1355-1366
Number of pages12
JournalExpert Opinion on Drug Delivery
Issue number12
Publication statusPublished - 2017 Dec 2


  • Anti-cancer fluoropyrimidine agent
  • FDA approval
  • dihydropyrimidine dehydrogenase inhibitor
  • fixed-dose combination drug
  • oral administration
  • prodrug

ASJC Scopus subject areas

  • Pharmaceutical Science


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