title: Correlation between the urinary dihydrouracil-uracil ratio and the 5-FU plasma concentration in patients treated with oral 5-FU analogs.
abstract: BACKGROUND
  The determination of dihydropyrimidine dehydrogenase (DPD) deficiency is important in avoiding severe 5-fluorouracil (FU) toxicity. The dihydrouracil (UH2)-uracil (Ura) ratio (UH2/Ura) in plasma might be an important indicator of the risk of 5-FU catabolic deficiency. In order to clarify this possibility, the pyrimidine metabolites and the UH2/Ura were measured in urine and the plasma level of 5-FU was evaluated in patients with gastric and colorectal cancer.
  
  
  METHODS
  Patients with primary gastric (n=14) and colorectal (n=8) cancer who had undergone surgery were recruited in this study. These patients were divided into the S-1 treatment group, which drug is a novel oral formulation of tegafur, oxonic acid and 5-chloro-2, 4-dihydroxypyridine (CDHP) (n=14) and a group receiving other drugs which include UFT (Uracil/Tegafur) or oral doxifluridine (n=8). The urinary levels of UH2 and Ura were measured by high-performance liquid chromatography (HPLC) using column swiching. The plasma level of 5-FU was assessed by gas chromatography-mass spectrometry (GC-MS).
  
  
  RESULTS
  The UH2/Ura or UH2/Ura (treated/no treated) in the S-1 group significantly decreased in comparison to that in the other-drug group and the plasma 5-FU concentration in the S-1 group significantly increased compared to that in the group treated with other drugs. The plasma 5-FU concentration levels significantly indicated a positive correlation with urinary Ura. Moreover, UH2/Ura treated with 5-FU analogs or UH2/Ura (treated/no treated) significantly showed a negative correlation with the plasma 5-FU concentration levels.
  
  
  CONCLUSIONS
  Our findings indicate that either urinary Ura, the UH2/Ura or UH2/Ura (treated/no treated) can predict the plasma 5-FU concentration levels or DPD deficiencies.
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kita-kyushu, Japan. nakayama@med.uoeh-u.ac.jp
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Inoue
authors.forename: Takefumi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Koji
authors.initials: K
authors.lastname: Kadowaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shibao
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tsurudome
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sako
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy; D014498:Uracil / Q000031:analogs & derivatives* / Q000652:urine*
chemical_list: C007419:dihydrouracil; D014498:Uracil; D005472:Fluorouracil