Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis
Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis
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DOI：
10.1007/s00228-012-1405-4
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Mahteme, H.
中科院分区：
文献类型：
--
作者：
Cashin, P. H.;Ehrsson, H.;Mahteme, H.
目的：顺铂在热腹腔化疗（HIPEC）中的应用以前没有用选择性技术进行过测量。主要目的是研究活性顺铂及其单水合复合物（MHC）在HIPEC过程中的药代动力学，比较顺铂的全身吸收与奥沙利铂，并比较活性顺铂水平的总platelet.Methods 10例患者进行细胞减灭术和HIPEC（顺铂50 mg/m2，阿霉素15 mg/m2）。在HIPEC期间和之后抽取血液和灌注液样品。结果顺铂灌流液的平均半衰期（t1/2）为18.4min，与电感耦合等离子体质谱（ICP-MS）法比较，顺铂的平均半衰期（t1/2）为18.4min，与电感耦合等离子体质谱（ICP-MS）法比较差异有显著性（P <0.05）。时间-浓度曲线下面积（AUC）0-90 min为2.87 mM.min，估计0-60 min为2.45 mM. min。顺铂的吸收t1/2为9.0 min，奥沙利铂为18.2 min。结论顺铂的吸收快于奥沙利铂，且随着灌注时间的延长，总铂量与活性顺铂的比值呈线性增加。将灌注时间降低至60 min不会显著改变顺铂的药代动力学，因此应予以考虑。随着HIPEC灌注的进行，ICP-MS技术不能充分反映灌注液中的活性顺铂水平。
Purpose Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has not previously been measured with a selective technique. The primary aims were to examine the pharmacokinetics of active cisplatin and its monohydrated complex (MHC) during HIPEC using a specific measuring technique, to compare cisplatin's systemic absorption with oxaliplatin, and to compare active cisplatin levels to that of total platinum.Methods Ten patients treated with cytoreductive surgery and HIPEC (cisplatin 50 mg/m(2), doxorubicin 15 mg/m(2)) were recruited. Blood and perfusate samples were drawn during and after HIPEC. Cisplatin analysis was conducted using liquid chromatography (LC) with post-column derivatization with diethyldithiocarbamate and compared with inductively coupled plasma-mass spectrometry (ICP-MS).Results The mean half-life (t1/2) of perfusate cisplatin was 18.4 min, with area under the time-concentration curve (AUC) 0-90 min of 2.87 mM.min and estimated 0-60 min of 2.45 mM.min. The absorption t1/2 was 9.0 min for cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active cisplatin increased in a linear manner by time of perfusion.Conclusions Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60 min does not significantly change the pharmacokinetics of cisplatin, and is therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS technique does not adequately reflect active cisplatin levels in the perfusate.