Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients.
OBJECTIVE
The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated.


METHODS
A dose of 40 mg/m(2) of S-1 was administered orally twice daily for 7 days (80 mg/m(2)/day) preoperatively in ten patients with resectable gastric cancer, and the same dose of S-1 was administered for 28 consecutive days after gastrectomy. Plasma concentrations of tegafur, gimeracil, and oteracil potassium, all the components of S-1, and 5-FU were measured on pre- and postoperative days. Concentrations of 5-FU in tumor and normal tissues were also determined.


RESULTS
At day 4 from the initial preoperative administration of S-1, the AUC of 5-FU was 1,055 +/- 304 ng h/ml. At day 18, day 28, and day 42 after gastrectomy, it was 1,012 +/- 331, 1,070 +/- 403, and 946 +/- 226 ng h/ml, respectively. No significant differences for plasma 5-FU were observed between pre- and postoperative days. In the resected tumor tissues, concentrations of 5-FU were 242 +/- 83 ng/g around 4.5 h and 91.7 +/- 37.0 ng/g around 20 h after the final administration, respectively.


CONCLUSIONS
Gastrectomy does not affect on pharmacokinetics of 5-FU derived from S-1 regardless of partial or total gastrectomy, indicating that S-1 can be a useful drug in postoperative adjuvant chemotherapy for gastric cancer.
Kochi
Mitsugu
M
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan. gann@med.nihon-u.ac.jp
Fujii
Masashi
M
Kanamori
Noriaki
N
Kaiga
Teruo
T
Aizaki
Kazuo
K
Takahashi
Toru
T
Takayama
Tadatoshi
T
D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D017024:Chemotherapy, Adjuvant; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000493:pharmacokinetics*; D011725:Pyridines / Q000493:pharmacokinetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D005641:Tegafur / Q000493:pharmacokinetics*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil; C104201:gimeracil