STUDY OF THE PHARMACOKINETICS OF MITOMYCIN-C IN HUMANS DURING INTRAPERITONEAL CHEMOHYPERTHERMIA WITH SPECIAL MENTION OF THE CONCENTRATION IN LOCAL TISSUES

The aim of this work is to estimate the 24-hour distribution and elimi nation of mitomycin C (MMC) during and after intraperitoneal chemohype rthermia (IPCH) in 18 patients (13 gastric adenocarcinoma, 3 pancreati c adenocarcinoma, 2 malignant mesothelioma) who received 60 mg MMC dur ing 90-120 min 6 liters of heating solution HS; (42-degrees-C) or HS f lowing at 0.4 liters/min a closed circuit. MMC assay in the serum, uri ne, HS and in local biopsies were performed by high performance liquid chromatography. The amount of MMC in HS decreased by 54.1 +/- 13.6% d uring IPCH. The maximum MMC levels in serum reached 0.4 +/- 0.18 mg/l 45 min after the start of IPCH, then rapidly decreased. Only 1.77 +/- 0.93 mg were recovered in urine in 24 h. These data are consistent wit h a large and rapid absorption, mostly in local tissue, demonstrated b y the level in 7 post-IPCH biopsies (8.3 +/- 7.6 mg/kg).