Kuwahara Akiko, Yamamori Motohiro, Nishiguchi Kohshi, Okuno Tatsuya, Chayahara Naoko, Miki Ikuya, Tamura Takao, Inokuma Tsubasa, Takemoto Yoshiji, Nakamura Tsutomu, Kataoka Kazusaburo, Sakaeda Toshiyuki
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Int J Med Sci. 2009 Sep 28;6(6):305-11. doi: 10.7150/ijms.6.305.
The effects of replacing cisplatin (CDDP) with cis-diammineglycolatoplatinum (nedaplatin, NDP), a second-generation platinum complex, on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated in Japanese patients with esophageal squamous cell carcinoma, who were treated with a definitive 5-FU/CDDP-based chemoradiotherapy.
Fifty-six patients were enrolled, 49 treated with CDDP and 7 treated with NDP. A course consisted of continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, infusion of CDDP or NDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5 PM on days 3, 10, 38 and 45, and at 5 AM on days 4, 11, 39 and 46.
The circadian rhythm in plasma concentrations of 5-FU observed in the case of CDDP was altered when NDP was used instead. The clinical response can be predicted by monitoring plasma concentrations of 5-FU in the CDDP group, but not in the NDP group.
在接受以5-氟尿嘧啶（5-FU）和顺铂（CDDP）为主的根治性放化疗的日本食管鳞状细胞癌患者中，研究用第二代铂类复合物顺二氨环丁烷羧酸铂（奈达铂，NDP）替代顺铂（CDDP）对5-氟尿嘧啶（5-FU）药代动力学的影响。
招募了56例患者，其中49例接受CDDP治疗，7例接受NDP治疗。一个疗程包括在第1至5天和第8至12天以400mg/m²/天的剂量持续输注5-FU，在第1天和第8天以40mg/m²/天的剂量输注CDDP或NDP，以及在第1至5天、第8至12天和第15至19天以2Gy/天的剂量进行放疗，间隔2周后重复第二个疗程。在第3、10、38和45天下午5点以及第4、11、39和46天上午5点通过高效液相色谱法测定5-FU的血浆浓度。
当使用NDP替代CDDP时，观察到的5-FU血浆浓度的昼夜节律发生了改变。在CDDP组中，通过监测5-FU的血浆浓度可以预测临床反应，但在NDP组中则不行。
