Kochi Mitsugu, Fujii Masashi, Kanamori Noriaki, Kaiga Teruo, Aizaki Kazuo, Takahashi Toru, Takayama Tadatoshi
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
Cancer Chemother Pharmacol. 2007 Oct;60(5):693-701. doi: 10.1007/s00280-007-0415-x. Epub 2007 Feb 15.
The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated.
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.
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.
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.
研究胃切除术后给予S-1对其药代动力学的影响。
10例可切除胃癌患者在术前每天口服40mg/m²的S-1，分两次给药，共7天（80mg/m²/天），胃切除术后连续28天给予相同剂量的S-1。在术前和术后测定血浆中替加氟、吉美嘧啶、奥替拉西钾（S-1的所有成分）及5-氟尿嘧啶（5-FU）的浓度。同时也测定肿瘤组织和正常组织中5-FU的浓度。
从术前首次给予S-1起第4天，5-FU的曲线下面积（AUC）为1055±304ng·h/ml。胃切除术后第18天、第28天和第42天，分别为1012±331、1070±403和946±226ng·h/ml。术前和术后血浆5-FU浓度无显著差异。在切除的肿瘤组织中，末次给药后约4.5小时5-FU浓度为242±83ng/g，约20小时为91.7±37.0ng/g。
无论部分或全胃切除，胃切除术均不影响S-1来源的5-FU的药代动力学，表明S-1可作为胃癌术后辅助化疗的有效药物。
