title: Evaluation of 5-FU plasma concentration by 13C breath test in patients treated with oral 5-FU analogs.
abstract: OBJECTIVE
  The objective of this study was to investigate the influence of digestive gastrointestinal absorption function on the pharmacokinetics of the orally-administered anticancer drug, Tegafur-gimestat-otastat potassium (TS-1), by measuring the plasma 5-fluorouracil (5-FU) concentration using stable isotope breath tests.
  
  
  METHODS
  Twenty-nine patients with progressive/recurrent digestive organ cancer were enrolled for this pharmacokinetic study, and blood samples were obtained from each patient. The area under-the-time-concentration curve between 0 and 480 min (AUC0-480 min), time-of-drug concentration peak (T(max)), maximum drug concentration (C(max)) and the half-life period (t(1/2)) of 5-FU were investigated. Simultaneously, a continuous (13)C-acetate breath test was performed for each patient. The parameters measured with the breath test were the area under the (13)CO(2) excretion rate curve between 0-4 h (AUC(0-4h)), peak (13)CO(2) value and elimination rate constant (K(el)) value.
  
  
  RESULTS
  The AUC(0-8h) and C(max) of 5-FU were significantly correlated with K(el) (p=0.012 and p=0.024, respectively), and the 5-FU C(max) value was significantly correlated with the peak value of (13)CO(2) (p=0.037). Multivariate regression analysis also found the C(max) of 5-FU to be associated with K(el) (p=0.0118). The C(max) and AUC(0-8h) of 5-FU were also significantly correlated (p<0.0001).
  
  
  CONCLUSIONS
  The results of this study suggest that gastrointestinal absorption is closely-related to plasma 5-FU concentration after oral administration of TS-1.
authors.affiliation: Department of Digestive Surgery, Kawasaki Medical School Kurashiki, Okayama, Japan. masahar@med.kawasaki-m.ac.jp
authors.forename: Masaharu
authors.initials: M
authors.lastname: Higashida
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Hisako
authors.initials: H
authors.lastname: Kubota
authors.forename: Haruaki
authors.initials: H
authors.lastname: Murakami
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oka
authors.forename: Hideo
authors.initials: H
authors.lastname: Okumura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hirai
mesh_terms: D000085:Acetates / Q000032:analysis / Q000493:pharmacokinetics; D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001944:Breath Tests; D002247:Carbon Isotopes / Q000032:analysis; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D010094:Oxonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000085:Acetates; D000964:Antimetabolites, Antineoplastic; D002247:Carbon Isotopes; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil