title: [Pharmacokinetics of S-1].
abstract: S-1 is an attractive oral fluorouracil antitumor drug, which is being called "a self-rescuing drug". This novel oral fluoropyrimidine is combined with three pharmacological agents: tegafur (FT) which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP) which inhibits dihydropyrimidine dehydrogenase (DPD) activity, and potassium oxonate (Oxo) which reduces gastrointestinal toxicity. Phase I and an early phase II clinical trials were performed about ten years ago, and these results had already been introduced to the Journal "Clinical Cancer Research Vol. 5, pages 2000-2005, 1999". The data of this article in this journal was referred from the results of the figures and tables based on the above trial. Most of the authors in this article have contributed on that pharmacokinetics study and published the above manuscripts. In that study, the pharmacokinetics of 5-FU, intact FT, CDHP and Oxo after administration of the standard dose of S-1 had been performed. These studies were carried out at two hospitals, Department of Surgery (Section 1) Sapporo Medical University and Chemotherapy Cancer Center, Cancer Institute Hospital and Japanese Foundation for Cancer Research (Ohtsuka). The number of patients accepted for this trial is twelve, 5 patients with gastric cancer, 4 with colorectal cancer and 3 with breast cancer. Single administration trial was referred to all patients, but consecutive administration trial was limited to ten patients. The results of plasma concentration, Cmax, Tmax, AUC0-14, and T1/2 of 5-FU, FT, CDHP, and Oxo were ascertained in details. It was a surprise that the indicated data was very similar to that of the intravenous 5-FU continuous infusion. Therefore, the low dose administration of 5-FU (FT) as S-1 may result in good antitumor effects with minimum adverse effects to the patients.
authors.affiliation: Dept of Surgery (Section 1), Sapporo Medical University, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Noboru
authors.initials: N
authors.lastname: Horikoshi
authors.forename: Kazusaku
authors.initials: K
authors.lastname: Tominaga
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sohma
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Okazaki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nakano
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ishizuka
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shinji
authors.initials: S
authors.lastname: Uno
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Taguchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamamitsu
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Shirasaka
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010094:Oxonic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014498:Uracil / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D014498:Uracil; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil