Correlation between the urinary dihydrouracil-uracil ratio and the 5-FU plasma concentration in patients treated with oral 5-FU analogs.
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.
Nakayama
Yoshifumi
Y
Department of Surgery 1, University of Occupational and Environmental Health, Kita-kyushu, Japan. nakayama@med.uoeh-u.ac.jp
Matsumoto
Kentaro
K
Inoue
Yuzuru
Y
Katsuki
Takefumi
T
Kadowaki
Koji
K
Shibao
Kazunori
K
Tsurudome
Yosuke
Y
Hirata
Keiji
K
Sako
Tatsuhiko
T
Nagata
Naoki
N
Itoh
Hideaki
H
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*
C007419:dihydrouracil; D014498:Uracil; D005472:Fluorouracil