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.
This study demonstrated that an assay of tumor OPRT contributes to the determination of 5-FU-based adjuvant chemotherapy outcome and application in clinical practice should be included in tumor analysis prior to 5-FU-based adjuvant chemotherapy.
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