Effect of gastrectomy on the pharmacokinetics of 5-fluorouracil and gimeracil after oral administration of S-1.
The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated in a total of 12 cases - nine in which partial gastrectomy was performed and three in which total gastrectomy was performed. A single oral dose of S-1, 50 mg as tegafur, was administered, serial peripheral blood samples were collected, and the concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured. The pre-operative S-1 dose was administered about 7 days before surgery and the post-operative dose was administered around post-operative hospital day 14. In the partial gastrectomy cases the maximum post-operative blood concentration (Cmax) of 5-FU and CDHP tended to be lower than before surgery, and the difference in 5-FU concentrations was significant. The area under the blood concentration-time curve (AUC0-8 h) for CDHP was significantly smaller post- than pre-operatively, but no significant difference was observed with regard to 5-FU. In the total gastrectomy cases the post-operative tmax of both 5-FU and CDHP was shorter than the pre-operative tmax, and no significant differences were observed between the pre- and post-operative AUC0-8 h values. Thus, the results of the present study showed that around post-operative hospital day 14, when total oral feeding had become possible after surgery for gastric cancer, the AUC0-8 h values of 5-FU and CDHP after S-1 administration were almost the same as before surgery and that gastrectomy had hardly any effect on the pharmacokinetics of S-1.
Department of Coloproctological Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Yuko
Y
Tsuruoka
Toshiki
T
Kamano
Masayuki
M
Kitajima
Ken
K
Kawai
Suguru
S
Watabe
Takumi
T
Ochiai
Kazuhiro
K
Sakamoto
Tetsuhiko
T
Shirasaka
D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000097:blood* / Q000493:pharmacokinetics; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil; C104201:gimeracil