Study of the Pharmacokinetics of Mitomycin C in Humans during Intraperitoneal Chemohyperthermia with Special Mention of the Concentration in Local Tissues

Abstract

The aim of this work is to estimate the 24-hour distribution and elimination of mitomycin C (MMC) during and after intraperitoneal chemohyperthermia (IPCH) in 18 patients (13 gastric adenocarcinoma, 3 pancreatic adenocarcinoma, 2 malignant mesothelioma) who received 60 mg MMC during 90-120 min in 6 liters of heating solution HS; (42 °C) or HS flowing at 0.4 liters/ min in a closed circuit. MMC assay in the serum, urine, HS and in local biopsies were performed by high performance liquid chromatography. The amount of MMC in HS decreased by 54.1 ± 13.6% during 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 with a large and rapid absorption, mostly in local tissue, demonstrated by the level in 7 post-IPCH biopsies (8.3 ± 7.6 mg/kg).