title: Impact of hyperthermia on pharmacokinetics of intraperitoneal mitomycin C in rats investigated by microdialysis.
abstract: OBJECTIVE
  Patients with peritoneal surface malignancies are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, commonly using mitomycin C (MMC). The purpose of this study was to investigate impact of hyperthermia on pharmacokinetics of intraperitoneal MMC.
  
  
  METHODS
  In 14 athymic nude male rats, microdialysis (MD) probes were implanted in jugular vein (V), hind leg muscle (M) and extraperitoneal space (XP). Probes were calibrated by retrodialysis. Intraperitonal chemotherapy perfusion (IPEC) was administered over 90 min with MMC 5 mg/kg and saline 0.9% 500 ml/kg at 35 and 41°C, defining the normothermic (NG) and hyperthermic groups (HG), respectively. MD and peritoneal perfusion fluid (PPF) samples were collected at 10 min intervals to determine MMC concentration.
  
  
  RESULTS
  Time-concentration curves were virtually parallel between temperature groups, with equal peak concentrations (µM) of 0.3 (V), 0.7 (XP) and 0.3 (M). The following area under time-concentration curve (AUC) ratios were calculated: AUC PPF/AUC V were 69 in NG and 79 in HG (P = 0.54); AUC XP/AUC V were 2.7 in NG and 2.6 in HG (P = 0.90).
  
  
  CONCLUSIONS
  IPEC provides high intraperitoneal MMC concentration and increased bioavailability in extraperitoneal tissue, combined with low systemic absorption. Hyperthermia at 41°C did not modify MMC pharmacokinetics.
authors.affiliation: Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway.
authors.forename: Olaf
authors.initials: O
authors.lastname: Sørensen
authors.forename: Anders Mikal
authors.initials: AM
authors.lastname: Andersen
authors.forename: Alexandr
authors.initials: A
authors.lastname: Kristian
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Giercksky
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D010478:Chemotherapy, Cancer, Regional Perfusion; D006614:Hindlimb; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D007601:Jugular Veins; D008297:Male; D017551:Microdialysis; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018482:Muscle, Skeletal; D010537:Peritoneum / Q000737:chemistry; D051381:Rats; D011923:Rats, Nude
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin
keywords: hyperthermia; intraperitoneal chemotherapy; microdialysis; mitomycin C; pharmacokinetics