title: [Combined determination of urine uracil levels and plasma 5-FU clearance for a simple order-made treatment with anticancer agents of FU derivative].
abstract: Individual differences exist in the pharmacodynamics of fluorouracil-derived anticancer agents, with circadian variability even in the same patient probably due to individual differences in the distribution of dihydrophrimidine dehydrogenase (DPD), a decomposing enzyme. Though DPD activity is usually determined in the liver or blood, a more simplified estimation of DPD activity has been recently attempted using urine uracil levels. However, because urine uracil level has the drawback of being easily affected by food ingestion or kidney function, in this study it was determined simultaneously with the determination of plasma 5-FU clearance after sustained instillation of 250 mg 5-FU, in order to estimate DPD activity more accurately. A correlation was observed between urine uracil levels and 5-FU clearance. In cases showing a baseline urine uracil level below 25.1 mumol/g. Creatinine, the blood concentration decreased due to large 5-FU clearance, with a tendency for diminished efficacy of FU-derived anticancer agents. In cases showing a baseline urine uracil level above 99.9 mumol/g. Creatinine, on the other hand, adverse reactions due to FU anticancer agents tended to become more serious. Since urine uracil level can be determined easily, it could be the first choice in screening to detect abnormal metabolism of fluorouracil-derived anticancer agents under present circumstances. By combining determination of urine uracil level with 5-FU clearance, it seems possible to predict adverse effects and the effective rate of these agents more accurately. Under existing circumstances, where genetic analysis remains unavailable as a general practice, the combined determination of urine uracil levels and plasma 5-FU clearance may be beneficial in developing order-made treatments in cancer chemotherapy.
authors.affiliation: Dept. of Pharmacy, Osaka Southrn National Hospital.
authors.forename: Shigehumi
authors.initials: S
authors.lastname: Morimoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tsujinaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawato
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shono
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tabuse
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakata
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uenaka
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D042943:Dihydrouracil Dehydrogenase (NADP); D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000097:blood* / Q000493:pharmacokinetics; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism; D014498:Uracil / Q000652:urine*
chemical_list: D000964:Antimetabolites, Antineoplastic; D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil