CONCENTRATIONS OF DOXORUBICIN AND ITS METABOLITES IN HUMAN AUTOPSY HEART AND OTHER TISSUES

Purpose. Since doxorubicin causes cardiotoxicity, we wished to assess relative concentrations of doxorubicin and its metabolites in cardiac tissues of patients who had been treated antemortem. We also wished to determine factors that correlate with human cardiac doxorubicin and d oxorubicinol concentrations. Patients and Methods. Autopsy tissues wer e collected from 35 patients who had received doxorubicin at any time antemortem, and were assayed by high pressure liquid chromatography. R esults. The major species found in human autopsy cardiac tissues were doxorubicinol (median, concentration 92 ng/g, range 0 to 484 ng/g), an d doxorubicin (median 58 ng/g, range 0-1665 ng/g). Other doxorubicin m etabolites were detected in cardiac tissues in < half the patients. Of ten organs studied, heart ranked fifth with respect to median doxorub icin concentration and ranked fourth with respect to median doxorubici nol concentration. By multiple stepwise regression analysis, factors m ost closely associated with cardiac doxorubicin concentrations were ti me from last treatment divided by dose intensity, serum total protein, albumin, and hemoglobin (negative correlations), Factors most closely associated with cardiac doxorubicinol concentrations were cumulative doxorubicin dose, total protein, hemoglobin, and uric acid (positive a ssociations), and respiratory rate (negative association). The physiol ogic significance of these associations (if any) is uncertain. By pair ed t-tests, cardiac doxorubicin and doxorubicinol concentrations were significantly (p < 0.05) higher than concentrations in skeletal muscle and smooth muscle organs.