Li T S, Kaneda Y, Saeki K, Ueda K, Zempo N, Esato K
First Department of Surgery, Yamaguchi University School of Medicine, Japan.
Eur J Cancer. 1999 Dec;35(13):1846-50. doi: 10.1016/s0959-8049(99)00226-9.
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 60 min with 25, 50 or 100 micrograms/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.
已进行离体肺灌注以治疗无法切除的肺肿瘤；然而，该操作的药代动力学仍不清楚。本研究旨在通过使用不同的灌注时间和灌注液药物浓度，研究离体肺灌注后肿瘤组织和肺组织中抗肿瘤药物浓度的变化。在大鼠建立孤立性肺肿瘤结节后，将离体左肺用25、50或100微克/毫升的顺铂灌注20、40或60分钟，并通过无焰原子吸收光谱法测定灌注肺组织和肿瘤组织中的总铂浓度。通过组织学检查和肺的湿重与干重比评估灌注肺组织中的水肿情况。肺组织中的总铂浓度随灌注时间和灌注液顺铂浓度的增加而显著增加，但肿瘤组织中的总铂浓度没有变化。灌注组之间肺组织的湿重与干重比没有显著差异。灌注肺组织的水肿情况不会随灌注时间或灌注液顺铂浓度而显著变化。本研究结果表明，顺铂离体肺灌注后肿瘤组织和肺组织之间可能存在不同的药代动力学，这可为选择合适的灌注时间和灌注液药物浓度提供临床指导。
