Adriamycin (
doxorubicin), an active
antineoplastic drug, is rapidly distributed across cell membranes and is concentrated within cells. Binding to
protein and to tissue readily occurs. The
drug is metabolized to both fluorescent and nonfluorescent compounds, the liver being the main organ of biotransformation and elimination. A multicompartment, open model that accounts for these processes has been derived. The model assumes an initial volume of distribution of 60% of
body weight and includes two peripheral
adriamycin compartments and a subsystem for
adriamycinol, a major metabolite. Plasma and urine concentrations of
adriamycin and
adriamycinol were determined for four patients treated with
adriamycin (60 mg/m2), and these concentrations were used to calculate rate constants for the model. Concentrations were measured by fluorescence assay after thin-layer chromatographic separation of parent compound and metabolites. Differential equations were solved by the SAAM computer program. Evaluation of adriamcinol pharmacokinetics suggests that the previously reported high concentrations of
adriamycinol immediately after IV infusion of
adriamycin are an artifact of the fluorescence method and that observed plasma concentrations of
adriamycinol are the sum of
adriamycinol concentrations and approximately 10% of the
adriamycin concentrations. Corrected peak plasma concentrations of
adriamycinol occur 2--12 h after infusion of
adriamycin.