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

Benny Weksler, Ng Bruce, Jeffrey T. Lenert, Michael E. Burt

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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.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalThe Annals of thoracic surgery
Volume56
Issue number2
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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Intravenous Injections
Doxorubicin
Perfusion
Lung
Weight Gain

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Surgery

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Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection. / Weksler, Benny; Bruce, Ng; Lenert, Jeffrey T.; Burt, Michael E.

In: The Annals of thoracic surgery, Vol. 56, No. 2, 01.01.1993, p. 209-214.

Research output: Contribution to journalArticle

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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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