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Reduction of drug leakage by negative-balance isolated pelvic perfusion: correlation between leakage and in-out flow rate in a pig model

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Abstract

Purpose: Isolated pelvic perfusion (IPP) therapy exposes target tissues to high doses of anticancer drugs with low systemic concentrations, but the major drawback is drug leakage into the systemic circulation, which often thwarts the increased drug concentration. In this study, the efficacy of altering the in-out flow rate during IPP in order to decrease the leakage was assessed in adult pigs. Methods: The abdominal aorta and the infrarenal vena cava were occluded with two balloon catheters, blood in the extracorporeal circuit was circulated with twin rotary pumps, and the IPP was performed with platinum. Three sets of in-out flow rates were used, and the degree of drug leakage into the systemic circulation was evaluated. The volume of blood withdrawn was equal to the volume returned (300 ml/min; group A), 5% higher (group B), or 10% higher (group C). The platinum concentrations in the pelvic circulation, systemic circulation, and urine were measured and compared. Results: The average and maximum plasma platinum concentrations in the pelvic circulation did not significantly differ among the three groups. The plasma platinum concentrations in the systemic venous circulation of the three groups significantly (P<0.01) decreased as the volume withdrawn during IPP increased. The percentage of platinum eliminated in the urine during IPP was significantly (P<0.01) lower in group B and C than in group A. Conclusions: Setting the volume withdrawn higher than the volume returned decreased leakage into the systemic circulation under isolated pelvic perfusion.

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Acknowledgements

This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceuticals and Medical Devices Agency (PMDA) and the Grant-in-Aid for Cancer Research (1, 14-5) from the Ministry of Health, Labour and Welfare.

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Correspondence to Satoru Murata.

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Murata, S., Tajima, H., Kusakai, G. et al. Reduction of drug leakage by negative-balance isolated pelvic perfusion: correlation between leakage and in-out flow rate in a pig model. J Cancer Res Clin Oncol 131, 575–580 (2005). https://doi.org/10.1007/s00432-004-0666-4

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Keywords

  • Isolated pelvic perfusion
  • Negative-balance isolated pelvic perfusion
  • Pig animal model