title: Plasma level of a 5-fluorouracil metabolite, fluoro-beta-alanine correlates with dihydropyrimidine dehydrogenase activity of peripheral blood mononuclear cells in 5-fluorouracil treated patients.
abstract: 5-fluorouracil (5-FU) is mostly metabolized after administration, and the metabolizing enzyme, dihydropyrimidine dehydrogenase (DPD), seems to be the rate-limiting factor. However, there are few reports on the final metabolite, fluoro-beta-alanine (FBAL). We report here the results of determination of the FBAL level in 5-FU treated patients and the correlation between the FBAL level and the DPD activity in peripheral blood mononuclear cells (PBMCs). Blood samples were collected from 20 patients, who had received continuous intravenous infusion (CIV) of 5-FU (320 mg/m2/24 hr) after resection of colorectal cancer, and the FBAL level was determined by high performance liquid chromatography (HPLC), after derivatizing into o-phthalaldehyde (OPA) and detecting fluorescence. DPD activity was measured in cytosol prepared from PBMCs using HPLC radioassay. The average FBAL plasma level during CIV of 5-FU was 911.0 ng/ml (521.0 to approximately 1834.6 ng/ml) and that of DPD activity in PBMCs was 282.6 pmol/min/mg-protein (145.0 to approximately 568.0 pmol/min/mg-protein). There was a significant correlation between the FBAL level and the DPD activity (r=0.805, p<0.0001). FBAL level in plasma may be useful in predicting the DPD activity in PBMCs, however, further studies are required considering the small number of cases in this study.
authors.affiliation: First Department of Surgery, Sapporo Medical University, Sapporo, Japan. furuhata@sapmed.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Furuhata
authors.forename: M
authors.initials: M
authors.lastname: Kawakami
authors.forename: K
authors.initials: K
authors.lastname: Okita
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: C
authors.initials: C
authors.lastname: Kihara
authors.forename: T
authors.initials: T
authors.lastname: Tsuruma
authors.forename: T
authors.initials: T
authors.lastname: Ohmura
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: F
authors.initials: F
authors.lastname: Hata
authors.forename: T
authors.initials: T
authors.lastname: Katsuramaki
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000368:Aged; D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009764:o-Phthalaldehyde / Q000494:pharmacology
chemical_list: C007742:3-fluoroalanine; D009764:o-Phthalaldehyde; D042943:Dihydrouracil Dehydrogenase (NADP); D000409:Alanine; D005472:Fluorouracil