Cerretani D, Nencini C, Urso R, Giorgi G, Marrelli D, De Stefano A, Pinto E, Cioppa T, Nastri G, Roviello F
Department of Pharmacology G. Segre, University of Siena, Siena, Italy.
J Chemother. 2005 Dec;17(6):668-73. doi: 10.1179/joc.2005.17.6.668.
Over the last few years surgery on patients with abdominal malignancies has become more aggressive but the majority of patients present locoregional recurrence as peritoneal dissemination. Cytoreductive surgery followed by intraperitoneal chemohyperthermic perfusion (ICHP) has been described for treatment and prevention of locoregional cancer spread from various origins. This paper reports our study of the pharmacokinetics of mitomycin C (MMC) administered by intraperitoneal chemohyperthermic perfusion (ICHP) in patients with peritoneal carcinomatosis. 28 patients received MMC 20 mg/m2 intraperitoneally as a perfusion over 60 min. MMC was determined in perfusate, plasma and urine samples with a UV-HPLC method. A compartmental model was used to fit the drug concentrations in plasma and perfusate. Our results showed a mean maximum plasma concentration (Cmax) of 0.14 +/- 0.086 microg/ml with a peak time (Tmax) of 48..7 +/- 5.61 min. The mean area under the curve (AUC) and terminal half-life (t1/2) were 15.8 +/- 9.8 mg x min/L and 83.7 +/- 31.74 min respectively. Clearance (CL) was estimated by fitting the data by a compartmental model and the mean value was 72 +/- 66 L/h. The percent of the dose absorbed was very variable and ranged between 14 and 57% (mean 37 +/- 14%). The mean percentage of dose recovered unchanged in the urine during 24 hours was 7.21 +/- 3.73%. We conclude that ICHP in patients with peritoneal surface malignancies seems to have clinical value since it gives high peritoneal and tumor MMC concentrations with limited systemic exposure and toxicity.
在过去几年中，腹部恶性肿瘤患者的手术治疗变得更加积极，但大多数患者会出现局部区域复发，表现为腹膜播散。已经描述了减瘤手术联合腹腔内热化疗灌注（ICHP）用于治疗和预防各种来源的局部区域癌症扩散。本文报告了我们对丝裂霉素C（MMC）通过腹腔内热化疗灌注（ICHP）给药在腹膜癌患者中的药代动力学研究。28例患者接受20mg/m²的MMC腹腔内灌注60分钟。采用紫外-高效液相色谱法测定灌注液、血浆和尿液样本中的MMC。使用房室模型拟合血浆和灌注液中的药物浓度。我们的结果显示，平均最大血浆浓度（Cmax）为0.14±0.086μg/ml，达峰时间（Tmax）为48.7±5.61分钟。平均曲线下面积（AUC）和末端半衰期（t1/2）分别为15.8±9.8mg·min/L和83.7±31.74分钟。通过房室模型拟合数据估计清除率（CL），平均值为72±66L/h。吸收剂量的百分比变化很大，范围在14%至57%之间（平均37±14%）。24小时内尿液中未改变回收的剂量平均百分比为7.21±3.73%。我们得出结论，腹膜表面恶性肿瘤患者的ICHP似乎具有临床价值，因为它能使腹膜和肿瘤中的MMC浓度升高，同时全身暴露和毒性有限。
