Drug delivery of oral anti-cancer fluoropyrimidine agents

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

来源：Expert Opinion on Drug Delivery, 2017, 14(12): 1355-1366.

DOI：10.1080/17425247.2017.1316260

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

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.

• 出版日期2017