Source: Annual Congress 2002 - Isolated lung perfusion and lung cancer
Disease area: Pulmonary vascular diseases

Abstract

Objective: Retrograde ILP with doxorubicin delivery via the pulmonary vein results in drug distribution to both, pulmonary artery- and bronchial artery-perfused territories in the rat lung. In this study, pharmacokinetics and toxicity of anterograde (a) and retrograde (r) ILP with doxorubicin were compared in the same animal model.
Methods: 3 groups of 16 Fischer rats underwent either left aILP or rILP with increasing doses of doxorubicin (I=20μg/ml, II=80μg/ml, III=320 μg/ml), followed by washout with hetastarch, and restoration of blood flow. Half of the animals of each group were followed up and weights were recorded for 4 weeks before a right pneumonectomy was performed to assess the toxicity of anterograde or retrograde perfusion on the left lung. All other animals were sacrificed after a blood reperfusion time of 60min after ILP. Doxorubicin levels in the effluent, the systemic blood and in the lung were determined by HPLC.
Results: All animals perfused with 320μg/ml survived ILP but not the opposite pneumonectomy. Rats perfused with 20 or 80μg/ml survived ILP and opposite pneumonectomy without significant differences in growthcurves up to 60 days after aILP or rILP. Pharmacokinetic analysis revealed maximum doxorubicin concentrations in the lung after aILP and rILP in group I of 14.1±]1.0 vs. 16.3±]5.7 μg/g, in group II of 43.3±]14.6 vs. 64.3±]6.6μg/g, and in group III of 119±]10.5 vs. 144±]28.2μg/g, respectively.
Conclusion: Doxorubicin-based aILP and rILP resulted in a similar toxicity in this model. With rILP a trend to a higher doxorubicin uptake in the lung was found.

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T. Krueger, A. Kümmerle, C. Vallet, Y. Pan, L. Decosterd, H. B. Ris (Lausanne, Switzerland). Anterograde and retrograde isolated lung perfusion (ILP) with doxorubicin in the rat: comparison of pharmacokinetics and toxicity. Eur Respir J 2002; 20: Suppl. 38, 1150

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