Doxorubicin distribution in human breast cancer.
Using a high-performance liquid chromatographic method coupled with fluorimetric detection, we evaluated plasma pharmacokinetics of doxorubicin (DX) and tissue distribution in seven patients suffering from locally advanced breast cancer. Tumor biopsies were performed 30 minutes and 24 hours after DX injection. In addition at 48 hours, during surgery, biopsies were obtained from primary breast cancer, nodes, and other accessible tissues, and DX concentrations were analyzed. A triexponential equation gave the best fit for plasma levels and the values (mean +/- SE) were: elimination half-life, 37.6 +/- 4.9 hours; volume of distribution, 605 +/- 61 L/m2; and clearance 200 +/- 27 ml/min/m2. There was greater interindividual variability in tumor DX concentrations than in plasma concentrations. DX reached much higher (range at 48 hrs, 1.54-14.17 micrograms/g) and longer-lasting concentrations in tumor than in plasma. At 48 hours tumor concentrations were 55.2-337.4 times the plasma concentrations. DX concentrations in normal breast were lower or similar to those in breast carcinoma. DX levels were very low in fat and skin, slightly higher in muscle, and very high in normal or metastasized lymph nodes.
Istituto di Recerche Farmacologiche Mario Negri, Milan, Italy.
C
C
Rossi
G
G
Gasparini
L
L
Canobbio
E
E
Galligioni
R
R
Volpe
E
E
Candiani
G
G
Toffoli
M
M
D'Incalci
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D014018:Tissue Distribution
D004317:Doxorubicin