TY - JOUR
T1 - Drug delivery of oral anti-cancer fluoropyrimidine agents
AU - Miura, Koh
AU - Shima, Hiroshi
AU - Takebe, Naoko
AU - Rhie, Julie
AU - Satoh, Kennichi
AU - Kakugawa, Yoichiro
AU - Satoh, Masayuki
AU - Kinouchi, Makoto
AU - Yamamoto, Kuniharu
AU - Hasegawa, Yasuhiro
AU - Kawai, Masaaki
AU - Kanazawa, Kousuke
AU - Fujiya, Tsuneaki
AU - Unno, Michiaki
AU - Katakura, Ryuichi
N1 - Funding Information:
Two studies introduced in this review [89,94] were supported by the Osaka Basic Medical Research Foundation (Osaka, Japan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/12/2
Y1 - 2017/12/2
N2 - 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.
AB - 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.
KW - Anti-cancer fluoropyrimidine agent
KW - FDA approval
KW - dihydropyrimidine dehydrogenase inhibitor
KW - fixed-dose combination drug
KW - oral administration
KW - prodrug
UR - http://www.scopus.com/inward/record.url?scp=85033409650&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033409650&partnerID=8YFLogxK
U2 - 10.1080/17425247.2017.1316260
DO - 10.1080/17425247.2017.1316260
M3 - Review article
C2 - 28379040
AN - SCOPUS:85033409650
VL - 14
SP - 1355
EP - 1366
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
SN - 1742-5247
IS - 12
ER -