title: Fixed dosing and pharmacokinetics of S-1 in Japanese cancer patients with large body surface areas.
abstract: BACKGROUND
  S-1 is an oral anticancer agent that combines tegafur (FT) with 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate. The recommended initial dose of S-1 is 120 mg/day for patients with a body surface area (BSA) of > or =1.5 m(2) in Japan.
  
  
  METHODS
  We examined the effects of using this fixed dose on the pharmacokinetics of FT, CDHP, and active 5-fluorouracil (5-FU) on the basis of actual BSA. The pharmacokinetics was compared between patients with a BSA of 1.5-1.75 m(2) and those with a BSA of > or =1.75 m(2).
  
  
  RESULTS
  The median areas under the time-concentration curves (AUCs) of 5-FU and CDHP were significantly lower in patients with a BSA of > or =1.75 m(2) than in those with a BSA of 1.5-1.75 m(2) (P = 0.005 and 0.006, respectively; Mann-Whitney U-test). There was no difference between the groups in the median AUC of FT.
  
  
  CONCLUSIONS
  Systemic exposure to 5-FU is significantly lower in Japanese cancer patients with a large BSA of >1.75 m(2) who received the recommended fixed dose of S-1.
authors.affiliation: Department of Medical Oncology, Saitama International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Hidaka, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujita
authors.forename: W
authors.initials: W
authors.lastname: Ichikawa
authors.forename: W
authors.initials: W
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Endo
authors.forename: F
authors.initials: F
authors.lastname: Nagashima
authors.forename: R
authors.initials: R
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Miya
authors.forename: K
authors.initials: K
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Kodama
authors.forename: Y
authors.initials: Y
authors.lastname: Sunakawa
authors.forename: M
authors.initials: M
authors.lastname: Narabayashi
authors.forename: K
authors.initials: K
authors.lastname: Miwa
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: K
authors.initials: K
authors.lastname: Kawara
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001830:Body Surface Area; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000208:ethnology; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid