洛铂用于结直肠癌术中腹腔灌注化疗的药代动力学研究

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（62 940.20±29 786.14）ng/mL，（58 635.50±29 220.12）ng/mL，（50 559.60±27 661.24）ng/mL，（23 873.90±20 655.82）ng/mL，（15 440.80±19 075.12）ng/mL，（14 382.20±21 208.10）ng/mL，（12 929.70±20 245.06）ng/mL，（10 775.30±19 995.77）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（1 788.402±1 543.580）h?ng/mL；引流液中洛铂最大药物浓度Cmax为（69 055.0±27 587.55）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（257 421.876±288 148.148）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。

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

ObjectiveTo study the pharmacokinetics of Lobaplatin in the course of intraoperative intraperitoneal perfusion chemotherapy in colorectal cancer. MethodsPoured 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. ResultsThe 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 (62 940.20±29 786.14) ng/mL, (58 635.50±29 220.12) ng/mL, (50 559.60±27 661.24) ng/mL, (23 873.90±20 655.82) ng/mL, (15 440.80±19 075.12) ng/mL, (14 382.20±21 208.10) ng/mL, (129 29.70±20 245.06) ng/mL, (10 775.30±19 995.77) 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 (1 788.402±1 543.580) h?ng/mL. The maximum drug concentration in the drainage solution was (69 055.0±27 587.55) 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 (257 421.876±288 148.148) h?ng/mL. ConclusionLobaplatin 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.