Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis

Abstract

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. 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). 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. 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.