氟尿嘧啶植入剂胃癌术后腹腔缓释化疗的药动学研究

Pharmacokinetics of fluorouracil implants by intraperitoneal controlled-release chemotherapy after radical gastrectomy for carcinoma of stomach

目的探讨胃癌患者应用氟尿嘧啶植入剂进行腹腔缓释化疗的药动学规律。方法 26例胃癌参试者,切除肿瘤后分别于淋巴引流区域、瘤床等部位植入氟尿嘧啶植入剂,每点100 mg,共1000 mg。术后分别在规定的时间点抽取血样,测定5-FU的浓度,进行药动学模型拟合。结果胃癌患者氟尿嘧啶植入剂腹腔缓释化疗的体内的过程为一室缓释模型,药动学方程:Ct=A1e-Ket+A2e-Kat+A3e-Krt,外周血药达峰时间及峰浓度分别为141 h及0.22μg.ml-1,门静脉血药达峰时间及峰浓度分别为120 h及0.43μg.ml-1,外周血循环中消除、吸收及缓释半衰期分别为145 h、0.29 h及76.5h。结论此种腹腔化疗方法的药动学特点和参数,可为临床合理应用氟尿嘧啶植入剂,进行胃癌切除术后的区域性化疗提供参考数据。

Objective To study the pharmacokinetics of fluorouracil implants in patients receiving intraperitoneal controlled-release chemotherapy for treating stomach cancer. Methods There were 26 patients enrolled, each was ap- plied a total dose of 1000rag fluorouracil with every 100rag of which implanted to lymphatic drainage area, tumor bed and other spots after radical gastrectomy for carcinoma of stomach respectively. Then the blood samples were collected in set time to determine the concentration of fluorouracil, and appropriate pharmacokinetics model was fitted. Results The pharmacokinetics in vivo was one compartment controlled-release model. The equation was： Ct=A1e^-Ket＋A2e^Kat＋A3e^krt. The peak time and corresponding peak concentration of peripheral blood were 141h and 0. 22μg·ml^-1 respectively. The peak time and corresponding peak concentration of portal vein blood were 120h and 0. 43μg·ml^-1 respectively. The half-lives of elimination, absorption and controlled-release in peripheral blood were 145h, 0. 29h and 76, 5h respectively. Conclusion This study provided the pharmacokinetic characteristics and parameters of the fluorouracil implants for clinical rational use and reference for the regional chemotherapy after radical gastrectomy for carcinoma of storeach