title: Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives, capecitabine and 5'-deoxy-5-fluorouridine (5'-DFUR).
abstract: OBJECTIVE
  Capecitabine is a three-step prodrug that was rationally designed to be a more effective and safer alternative to its intermediate metabolite, 5'-deoxy-5-fluorouridine (5'-DFUR). We compared the pharmacokinetics/pharmacodynamics of these drugs in metastatic breast cancer patients.
  
  
  METHODS
  Six patients received oral capecitabine at 1657 mg/m2 twice daily and 17 received 5'-DFUR at 400 mg three times daily. Both drugs were administered for 21 days followed by a 7-day rest.
  
  
  RESULTS
  Median daily 5'-DFUR AUC was significantly higher for capecitabine than for 5'-DFUR (81.1 vs 32.6 mmol h/l; P = 0.01). Following treatment with 5'-DFUR, the median AUC and Cmax of 5'-DFUR tended to be higher in patients with a partial response (3.83 microg h/ml and 4.88 microg/ml) and stable disease (6.46 microg h/ml and 4.96 microg/ml) than in those with disease progression (2.53 microg h/ml and 1.36 microg/ml). The AUC and Cmax of 5'-DFUR was significantly related to overall survival.
  
  
  CONCLUSIONS
  These results support the superiority of capecitabine over 5'-DFUR.
authors.affiliation: Division of Oncology/Hematology, Department of Medicine, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ebi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sigeoka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawada
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Usubuchi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D005467:Floxuridine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; C025034:doxifluridine