Alternative pharmacokinetics of S‐1 components, 5‐fluorouracil, dihydrofluorouracil and α‐fluoro‐β‐alanine after oral administration of S‐1 following total gastrectomy

We studied whether total gastrectomy for gastric cancer would affect the pharmacokinetics of 5‐fluorouracil (5‐FU) and its degradation products, such as dihydrouracil (FUH 2 ) and α‐fluoro‐β‐alanine (FBAL), after oral administration of the fluorouracil derivative S‐1, composed of tegafur, 5‐chloro‐2,4‐dihydroxypyridine (CDHP; a dihydropyrimidine dehydrogenase inhibitor) and potassium oxonate. Blood and urine samples were obtained, both preoperatively and at least 2 weeks postoperatively, from six patients with advanced gastric cancers who were undergoing total gastrectomy. Plasma levels of tegafur, 5‐FU, CDHP, potassium oxonate, FUH 2 and FBAL were measured prior to and at 1, 2, 4, 6 and 10 h after oral administration of 40 mg/m 2 S‐1. The total amounts of 5‐FU, FUH 2 and FBAL excreted into urine during the 24‐h period after S‐1 administration were also measured. Total gastrectomy significantly increased the maximum concentration and the area under the curve until 10 h after administration (AUC 1–10h ) of plasma 5‐FU. The plasma AUC 1–10h of CDHP was significantly higher than the preoperative value. In terms of clinical efficacy, the higher AUC 1–10h of 5‐FU after total gastrectomy may be beneficial to S‐1 administered as adjuvant chemotherapy, and might be caused by the higher postoperative AUC 1–10h of CDHP relative to preoperative values. However, the dose of S‐1 for patients who have undergone total gastrectomy might be diminished to avoid severe adverse events and to continue the treatment for a long period. ( Cancer Sci 2007; 98: 1604–1608)