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 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 degrees 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).
Department of Biochemistry, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
G
G
Panteix
M
M
Guillaumont
L
L
Cherpin
J
J
Cuichard
F N
FN
Gilly
P Y
PY
Carry
A
A
Sayag
B
B
Salle
A
A
Brachet
J
J
Bienvenu
D000042:Absorption; D000230:Adenocarcinoma / Q000378:metabolism* / Q000628:therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D008297:Male; D008654:Mesothelioma / Q000378:metabolism* / Q000628:therapy; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000628:therapy; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000628:therapy
D016685:Mitomycin