Pharmacokinetic differences between rat tumour and lung tissues following isolated lung perfusion with cisplatin

Abstract

Isolated lung perfusion has been performed for the treatment of unresectable lung tumours; however, the pharmacokinetics of this procedure remain unclear. This study was conducted to investigate the changes in antitumour drug concentrations in tumour and lung tissues after isolated lung perfusion, using different perfusion times and perfusate drug concentrations. Isolated left lungs were perfused for 20, 40 or 60min with 25, 50 or 100μg/ml of cisplatin after solitary lung tumour nodules were established in rats, and the total platinum concentrations in the perfused lung and tumour tissues were determined by flameless atomic absorption spectroscopy. The oedema in the perfused lung tissues was evaluated by histological examination and by the wet to dry weight ratios of the lungs. The total platinum concentration increased significantly with perfusion time and increasing perfusate cisplatin concentrations in the lung tissue, but it did not change in the tumour tissue. The wet to dry weight ratios of the lung tissues did not differ significantly among the perfusion groups. Oedema of the perfused lung tissue did not change significantly with the perfusion time or perfusate cisplatin concentration. The results of this study indicate the possibility that different pharmacokinetics exist between tumour and lung tissues following isolated lung perfusion with cisplatin, which could be used as a clinical guide for the selection of appropriate perfusion times and perfusate drug concentrations.