洛铂用于结直肠癌术中腹腔灌注化疗的药代动力学研究  

The study on Lobaplatin pharmacokinetics of intraoperative intraperitoneal perfusion chemotherapy in colorectal cancer

作　　者：张睿[1] 石刚[1] 杨世华 苏昊 周思成 裴炜 梁建伟 刘正 关旭 赵志勋 刘骞 周志祥 王锡山 张景 周海涛 Zhang Rui;Shi Gang;Yang Shihua;Su Hao;Zhou Sicheng;Pei Wei;Liang Jianwei;Liu Zheng;Guan Xu;Zhao Zhixun;Liu Qian;Zhou Zhixiang;Wang Xishan;Zhang Jing;Zhou Haitao(Department of Colorectal Surgery,Liaoning Cancer Hospital&Institute,Shenyang 110042,China;Department of Abdominal Surgery,Cancer Hospital of HuanXing Chaoyang District Beijing,Beijing 100122,China;Department of Colorectal Surgery,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]辽宁省肿瘤医院结直肠外科,沈阳110042 [2]北京市朝阳区桓兴肿瘤医院腹部外科,100122 [3]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院结直肠外科,北京100021

出　　处：《中华结直肠疾病电子杂志》2020年第2期144-149,共6页Chinese Journal of Colorectal Diseases(Electronic Edition)

基　　金：中国癌症基金会北京希望马拉松基金(No.LC2016B10);中国医学科学院医学与健康科技创新工程(协同创新团队项目)(No.2017-I2M-4-002);北京协和医学院2018年度研究生创新基金项目(No.2018-1002-02-26);2018年度北京市东城区优秀人才计划。

摘　　要：目的研究洛铂用于预防性结直肠癌术中腹腔灌洗化疗过程中的药代动力学变化规律,为临床治疗提供参考依据。方法将含有120 mg/L浓度的洛铂溶液,在结直肠癌手术结束时灌入患者盆腹腔中,采集不同时点静脉血及腹腔引流液,应用LC_MS/MS方法,测定洛铂在血液和腹腔引流液中各时点药物浓度。结果11例患者灌注洛铂后0 h,0.5 h,l h,2 h,3 h,4 h,6 h,10 h,24 h,检测静脉血中洛铂的平均药物浓度分别为(333.50±333.00)ng/mL,(428.40±321.98)ng/mL,(425.90±347.70)ng/mL,(318.20±291.92)ng/mL,(198.90±196.85)ng/mL,(158.40±186.53)ng/mL,(68.90±66.06)ng/mL,(21.50±19.10)ng/mL,(6.70±0.00)ng/mL;腹腔引流液中洛铂的平均药物浓度分别为(62940.20±29786.14)ng/mL,(58635.50±29220.12)ng/mL,(50559.60±27661.24)ng/mL,(23873.90±20655.82)ng/mL,(15440.80±19075.12)ng/mL,(14382.20±21208.10)ng/mL,(12929.70±20245.06)ng/mL,(10775.30±19995.77)ng/mL,(64.00±111.93)ng/mL。洛铂在结直肠癌患者血浆中药动学符合二室模型拟合,各药动学参数分别为:最大血药浓度Cmax为(532.65±383.76)ng/mL,消除半衰期(t1/2z)为(1.84±0.32)h,药-时曲线下面积AUC(0-t)为(1788.402±1543.580)h?ng/mL;引流液中洛铂最大药物浓度Cmax为(69055.0±27587.55)ng/mL,消除半衰期(t1/2z)为(5.994±8.397)h;药-时曲线下面积AUC(0-t)为(257421.876±288148.148)h?ng/mL。结论洛铂腹腔灌洗化疗在腹腔中可持久维持较高的有效药物浓度,且血液吸收少,从而副作用较少,安全可靠,值得进一步研究。Objective To study the pharmacokinetics of Lobaplatin in the course of intraoperative intraperitoneal perfusion chemotherapy in colorectal cancer.Methods Poured the lobaplatin solution with120 mg/L into the pelvic and abdominal cavity after operation,Collected venous blood and its abdominal drainage fluid at different time points.LC_MS/MS method was used to determine the drug concentration of Lobaplatin in blood and abdominal drainage fluid.Results The mean concentrations of lobaplatin at 0 h,0.5 h,1 h,2 h,3 h,6 h,10 h and 24 h after infusion were(333.50±333.00)ng/mL,(428.40±321.98)ng/mL,(425.90±347.70)ng/mL,(318.20±291.92)ng/mL,(198.90±196.85)ng/mL,(158.40±186.53)ng/mL,(68.90±66.06)ng/mL,(21.50±19.10)ng/mL,(6.70±0.00)ng/mL,respectively.the mean concentration in the celiac drainage was(62940.20±29786.14)ng/mL,(58635.50±29220.12)ng/mL,(50559.60±27661.24)ng/mL,(23873.90±20655.82)ng/mL,(15440.80±19075.12)ng/mL,(14382.20±21208.10)ng/mL,(12929.70±20245.06)ng/mL,(10775.30±19995.77)ng/mL,(64.00±111.93)ng/mL.The pharmacokinetics of Lobaplatin accords with two-compartment model fitting in the pharmacokinetics of plasma traditional Chinese medicine in patients with colorectal cancer.The pharmacokinetic parameters were as follows:the maximum plasma concentration(Cmax)was(532.65±383.76)ng/mL,the elimination half-life(t1/2z)was(1.84±0.32)h,and the area AUC(0-t)under the drug-time curve was(1788.402±1543.580)h?ng/mL.The maximum drug concentration in the drainage solution was(69055.0±27587.55)ng/mL,the elimination half-life(t1/2z)was(5.994±8.397)h,and the area AUC(0-t)under the drug-time curve was(257421.876±288148.148)h?ng/mL.Conclusion Lobaplatin intraperitoneal irrigation chemotherapy can maintain a high effective drug concentration in the abdominal cavity with less blood absorption,and fewer side effects,which can be used as an effective treatment method to prevent metastasis of colorectal cancer.

关 键 词：结直肠肿瘤 药代动力学 手术 洛铂 腹腔化疗 术中化疗 

分 类 号：R969.1[医药卫生—药理学]