Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives, capecitabine and 5'-deoxy-5-fluorouridine (5'-DFUR).
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.
Ebi
Hiromichi
H
Division of Oncology/Hematology, Department of Medicine, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Sigeoka
Yasushi
Y
Saeki
Toshiaki
T
Kawada
Kenji
K
Igarashi
Tadahiko
T
Usubuchi
Noriko
N
Ueda
Ryuzo
R
Sasaki
Yasutsuna
Y
Minami
Hironobu
H
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
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; C025034:doxifluridine