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Open Access Research article

Validation and use of microdialysis for determination of pharmacokinetic properties of the chemotherapeutic agent mitomycin C - an experimental study

Olaf Sørensen1*, Anders Andersen2, Harald Olsen2, Kristian Alexandr3, Per Olaf Ekstrøm1, Karl-Erik Giercksky14 and Kjersti Flatmark13

Author Affiliations

1 Department of Surgical Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway

2 Department of Clinical Pharmacology, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway

3 Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway

4 Norwegian Radium Hospital Faculty Division, University of Oslo, 0310 Oslo, Norway

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BMC Cancer 2010, 10:469  doi:10.1186/1471-2407-10-469

Published: 1 September 2010

Abstract

Background

Mitomycin C is a chemotherapeutic agent used in the treatment of peritoneal surface malignancies, administered as hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. Pharmacokinetic studies have been based on analyses of blood, urine and abdominal perfusate, but actual tissue concentrations of the drug have never been determined. Microdialysis is an established method for continuous monitoring of low-molecular substances in tissues, and in the present study microdialysis of mitomycin C was studied in vitro and in vivo.

Methods

Using in vitro microdialysis, relative recovery was determined when varying drug concentration, temperature and perfusion flow rate. In vivo microdialysis was performed in rats to verify long-term stability of relative recovery in four compartments (vein, peritoneum, extraperitoneal space and hind leg muscle). Subsequently, intravenous and intraperitoneal bolus infusion experiments were performed and pharmacokinetic parameters were calculated.

Results

In vitro, compatibility of mitomycin C and microdialysis equipment was demonstrated, and relative recovery was stable over an adequate concentration range, moderately increased by raising medium temperature and increased when flow rate was reduced, all according to theory. In vivo, stable relative recovery was observed over seven hours. Mitomycin C exhibited fast and even distribution in rat tissues, and equal bioavailability was achieved by intravenous and intraperitoneal infusion. The half-life of mitomycin C calculated after intravenous infusion was 40 minutes.

Conclusions

Mitomycin C concentration can be reliable monitored in vivo using microdialysis, suggesting that this technique can be used in pharmacokinetic studies of this drug during hyperthermic intraperitoneal chemotherapy.