Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients

Abstract

Purpose: The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated. Patients and 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. Conclusion: 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. © 2007 Springer-Verlag.