ISOLATED SINGLE-LUNG PERFUSION WITH DOXORUBICIN IS PHARMACOKINETICALLY SUPERIOR TO INTRAVENOUS-INJECTION

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 eva luate lung tissue levels of doxorubicin, 35 rats were randomized into seven groups (n = 5). The first five groups underwent isolated lung pe rfusion with 72.1 +/- 6.9, 118.4 +/- 12.1, 255.2 +/- 12.8, 384.1 +/- 4 6.2, and 457.6 +/- 32.5 mug/mL of doxorubicin, respectively, for 10 mi nutes. Groups 6 and 7 received 5 mg/kg and 7 mg/kg of intravenous doxo rubicin, respectively. A second study was designed to measure heart ti ssue level of doxorubicin in 3 groups of 5 rats each. Two groups recei ved 5 or 7 mg/kg of intravenous doxorubicin and a third group underwen t isolated lung perfusion with 255.2 +/- 12.8 mug/mL of doxorubicin fo r 10 minutes. A third study, designed to evaluate toxicity in vivo, ha d a similar design, and the animals were followed up for 21 days after treatment. Lung doxorubicin concentration after isolated lung perfusi on 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 mug/mL than after 5 or 7 mg/kg of intravenous doxorubicin, respectively. Heart concentration of doxorubicin was significantly lower after isolated lung perfusion wit h 255.2 +/- 12.8 mug/mL of doxorubicin as compared with 5 or 7 mg/kg o f intravenous doxorubicin (p < 0.001). Animals that had systemic intra venous doxorubicin failed to gain weight as compared with animals afte r isolated lung perfusion (p < 0.006). In conclusion, isolated lung pe rfusion with doxorubicin is pharmacokinetically superior to systemic i ntravenous doxorubicin in this model.