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Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection
Journal article   Open access   Peer reviewed

Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection

Benny Weksler, Ng Bruce, Jeffrey T. Lenert and Michael E. Burt
The Annals of thoracic surgery, v 56(2), pp 209-214
01 Aug 1993
DOI: https://doi.org/10.1016/0003-4975(93)91149-H
PMID: 8347000
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/0003-4975(93)91149-HView
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Abstract

To investigate new modalities in the treatment of pulmonary metastases we developed a model of isolated singlelung perfusion in the rat. In this study we compare the pharmacokinetics of isolated lung perfusion and intravenous doxorubicin. In the first experiment, designed to evaluate lung tissue levels of doxorubicin, 35 rats were randomized into seven groups (n = 5). The first five groups underwent isolated lung perfusion with 72.1 ± 6.9, 118.4 ± 12.1, 255.2 ± 12.8, 384.1 ± 46.2, and 457.6 ± 32.5 μg/mL of doxorubicin, respectively, for 10 minutes. Groups 6 and 7 received 5 mg/kg and 7 mg/kg of intravenous doxorubicin, respectively. A second study was designed to measure heart tissue level of doxorubicin in 3 groups of 5 rats each. Two groups received 5 or 7 mg/kg of intravenous doxorubicin and a third group underwent isolated lung perfusion with 255.2 ± 12.8 μg/mL of doxorubicin for 10 minutes. A third study, designed to evaluate toxicity in vivo, had a similar design, and the animals were followed up for 21 days after treatment. Lung doxorubicin concentration after isolated lung perfusion was significantly higher than after intravenous doxorubicin ( p < 0.01). Tissue doxorubicin concentration was 25 and 20 times higher after isolated lung perfusion with 255.2 ± 12.8 μg/mL than after 5 or 7 mg/kg of intravenous doxorubicin, respectively. Heart concentration of doxorubicin was significantly lower after isolated lung perfusion with 255.2 ± 12.8 μg/mL of doxorubicin as compared with 5 or 7 mg/kg of intravenous doxorubicin ( p < 0.001). Animals that had systemic intravenous doxorubicin failed to gain weight as compared with animals after isolated lung perfusion ( p < 0.006). In conclusion, isolated lung perfusion with doxorubicin is pharmacokinetically superior to systemic intravenous doxorubicin in this model.

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Web of Science research areas
Cardiac & Cardiovascular Systems
Respiratory System
Surgery
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