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腹腔内温热灌注(IPHP)化疗是防治胃肠道癌术后复发的新途径。研究目的:探讨丝裂霉素C(MMC)用于术中IPHP化疗防治中晚期大肠癌术后复发的药代动力学及与临床疗效的关系。方法:19例初次治疗的中晚期大肠癌病人手术切除肿瘤后,通过加温灌注抗癌仪将溶有80mgMMC的生理盐水8000ml连续灌注人腹腔,保持腹腔内温度恒定(43~45℃),持续60min。用高效液相色谱法(HPLC)测定血清、尿、灌注液和局部组织浓度。观察血、尿中MMC的动态变化。血药浓度经GSP程序模拟出药代动力学模型并计算各药动学参数。结果:IPHP化疗前后灌注液中MMC减少(15.49±4.21)mg。血药浓度在灌注终止时达到降值(123.86±67.06)ng/ml,然后迅速下降。腹腔局部组织浓度高于(765.1±206.9)ng/ml。24h尿中仅排出(1.46±1.24)ng/ml MMC。全组病例的药代动力学模型为一室模型。血药时曲线下面积为(237.88±139.30)ng/ml·h~(-1)。消除半衰期为(61.2±18.6)min。结论:IPHP化疗局部药物浓度高,有利于癌细胞摄取更多的化疗药物,疗效高。血药浓度低,消除快,全身毒副作用小。
Intraperitoneal hyperthermic perfusion (IPHP) chemotherapy is a new way to prevent postoperative recurrence of gastrointestinal cancer. Objective: To investigate the relationship between the pharmacokinetics of mitomycin C (MMC) for the prevention and treatment of postoperative recurrence of advanced colorectal cancer with intraoperative IPHP chemotherapy and its relationship with clinical efficacy. Methods: Nineteen patients with primary and advanced colorectal cancer were treated by surgical resection of tumor. The rats were perfused with 8000ml of normal saline (80ml), and the intraperitoneal temperature was kept constant (43-45 ℃) 60min. Serum, urine, perfusate and local tissue concentrations were determined by high performance liquid chromatography (HPLC). Observe the dynamic changes of MMC in blood and urine. The plasma concentration of GSP program simulated pharmacokinetic model and calculate the pharmacokinetic parameters. Results: MMC in perfusion fluid before and after IPHP chemotherapy decreased (15.49 ± 4.21) mg. Blood concentration decreased to (123.86 ± 67.06) ng / ml at the end of perfusion and then rapidly decreased. The peritoneal tissue concentration was higher than (765.1 ± 206.9) ng / ml. Only 24h excreted (1.46 ± 1.24) ng / ml MMC in 24h urine. The pharmacokinetic model of all the patients was a one-compartment model. The blood plasma area under the curve (237.88 ± 139.30) ng / ml · h ~ (-1). Elimination half-life was (61.2 ± 18.6) min. Conclusion: High concentration of IPHP chemotherapy for local drug is conducive to cancer cells uptake of more chemotherapy drugs, high efficacy. Low blood concentration, eliminate fast, systemic side effects.