title: Effects of a low-fat meal on the oral bioavailability of UFT and leucovorin in patients with colorectal cancer.
abstract: BACKGROUND
  UFT is composed of tegafur, a prodrug of 5-fluorouracil, and uracil, at a fixed ratio of 1: 4. UFT is widely used with leucovorin as adjuvant chemotherapy in patients with colon cancer. As reported, UFT/leucovorin should not be taken simultaneously with food because a high fat content will reduce the systemic exposure to the active cytotoxic moiety of UFT. In this single-dose, randomized, two-way crossover study, we investigated the effects of a low-fat Japanese meal on the pharmacokinetics and oral bioavailability of UFT (2 x 100-mg capsules; dose in terms of tegafur) and leucovorin (1 x 25-mg tablet).
  
  
  METHODS
  Patients (n = 12) were randomly assigned to receive both drugs after an overnight fast or 5 min after eating a standard Japanese breakfast (641 kcal), with a 3-day washout period between treatments. Pharmacokinetics (n = 12) were determined for tegafur, 5-fluorouracil, uracil, leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin).
  
  
  RESULTS
  For 5-fluorouracil pharmacokinetics, the maximum plasma concentration and the area under the curve were reduced by 73.7% and 47.4%, respectively, when UFT was taken postprandially, and the maximum plasma concentration and the area under the curve for uracil were reduced by 84.1% and 68.9%, respectively, compared with dosing on an empty stomach. These decreases in the systemic exposure to 5-fluorouracil were quite marked and may have an impact on its antitumor effect.
  
  
  CONCLUSIONS
  A low-fat meal affects the pharmacokinetics of UFT similarly to a high-fat meal.
authors.affiliation: First Department of Surgery, Sapporo Medical University, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan. furuhata@sapmed.ac.jp
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Makoto
authors.initials: M
authors.lastname: Meguro
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nishidate
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.forename: Gentarou
authors.initials: G
authors.lastname: Ishiyama
authors.forename: Yuuji
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Tsuruma
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Toru
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018752:Diet, Fat-Restricted; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics; D014498:Uracil / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D011355:Prodrugs; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin