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 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)
Weksler
B
B
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Ng
B
B
Lenert
J T
JT
Burt
M E
ME
D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D009206:Myocardium / Q000737:chemistry; D011651:Pulmonary Artery; D051381:Rats; D011916:Rats, Inbred F344
D004317:Doxorubicin