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The Annals of Thoracic Surgery, Vol 56, 209-214, Copyright © 1993 by The Society of Thoracic Surgeons
B Weksler, B Ng, JT Lenert and ME Burt
To investigate new modalities in the treatment of pulmonary metastases we
developed a model of isolated single-lung 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
micrograms/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 micrograms/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 micrograms/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
micrograms/mL of doxorubicin as compared with 5 or 7 mg/kg of intravenous
doxorubicin (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Isolated single-lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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