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[胃癌患者口服S-1辅助化疗后5-氟尿嘧啶的药代动力学]

[Pharmacokinetics of 5-FU after S-1 oral administration for adjuvant chemotherapy in gastric cancer patients].

作者信息

Matsumoto Hideo, Hirai Toshihiro, Hirabayashi Yohko, Murakami Haruaki, Higashida Masaharu, Kawabe Yukiko, Fuchimoto Michihisa, Fujikura Hiroyuki, Hato Shinji, Urakami Atsushi, Yamashita Kazuki, Tsunoda Tsukasa

机构信息

Department of Surgery, Division of Gastroenterology, Kawasaki Medical School.

出版信息

Gan To Kagaku Ryoho. 2007 Jun;34(6):869-73.

Abstract

We studied the pharmacokinetics of 5-FU after S-1 oral administration at the usual dose (80 mg/m2) for adjuvant chemotherapy in 13 advanced gastric cancer patients (Stage II, III), and at a decreased dose (60 mg/m2) for adjuvant or combined chemotherapy in 13 advanced gastric cancer patients. Pharmacokinetic parameters of 5-FU in the serum were as follows: Cmax, 159 .9 2+/-45.2 ng/mL, Tmax, 2.17+/-0.58 h;T1/2, 3.13+/-2.88 h; and AUC(0-8), 768.0+/-260.8 ng h/mL in the patients with the usual dose, and Cmax, 117.3+/-55.1 ng/mL; Tmax, 2.62+/-0.9 6 h; T1/2, 3.09+/-1.9 5 h and AUC(0-8), 565.9+/-216.8 ng h/mL in the patients with the decreased dose. No difference in AUC was observed between operative methods. Adverse events of more than grade 3 were recognized in 7 patients, and AUC of 6 patients were more than 800 ng h/mL. The plasma concentration of 5-FU was quite different between patients. The difference of Cmax and AUC was 3-4 times. It was concluded that we must pay attention to individual differences in the plasma concentration of 5-FU in postoperative gastric cancer patients when S-1 would be administered.

摘要

我们研究了13例晚期胃癌患者(II期、III期)接受S-1口服常规剂量(80mg/m²)辅助化疗以及13例晚期胃癌患者接受S-1口服降低剂量(60mg/m²)辅助或联合化疗后5-氟尿嘧啶(5-FU)的药代动力学。血清中5-FU的药代动力学参数如下:常规剂量组患者的Cmax为159.92±45.2ng/mL,Tmax为2.17±0.58小时,T1/2为3.13±2.88小时,AUC(0-8)为768.0±260.8ng·h/mL;降低剂量组患者的Cmax为117.3±55.1ng/mL,Tmax为2.62±0.96小时,T1/2为3.09±1.95小时,AUC(0-8)为565.9±216.8ng·h/mL。不同手术方式之间未观察到AUC有差异。7例患者出现3级以上不良事件,6例患者的AUC超过800ng·h/mL。患者之间5-FU的血浆浓度差异很大。Cmax和AUC的差异为3至4倍。得出的结论是,在对术后胃癌患者使用S-1时,必须注意5-FU血浆浓度的个体差异。

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