Drug delivery of oral anti-cancer fluoropyrimidine agents.

Abstract:

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.

journal_name

Expert Opin Drug Deliv

authors

Miura K,Shima H,Takebe N,Rhie J,Satoh K,Kakugawa Y,Satoh M,Kinouchi M,Yamamoto K,Hasegawa Y,Kawai M,Kanazawa K,Fujiya T,Unno M,Katakura R

doi

10.1080/17425247.2017.1316260

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

1355-1366

issue

12

eissn

1742-5247

issn

1744-7593

journal_volume

14

pub_type

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