Plasma and tissue levels of doxorubicin (DXR) and doxorubicinol (DXR-OL) were measured fluorometrically after high-pressure liquid chromatography at 1, 3, and 24 h following one, nine, and 24 doses of 1.0 mg DXR/kg or one and eight doses of 4.0 mg DXR/kg, IP, to rats. Comparison of plasma levels of DXR found following single and multiple doses suggests significant build-up of DXR at 1 h with successive doses, but not at 3 h. Liver exhibited substantially higher levels of DXR (on a per gram of protein basis) than did plasma, and multiple doses did not produce higher levels than did a single dose. In contrast, the heart accumulated DXR slowly, attaining levels after multiple dosing in excess of those found in the liver. Skeletal muscle exhibited dose-related levels similar to those for heart but the absolute levels of DXR in muscle were only about one-tenth of those observed in heart. DXR-OL was at very low levels of less than or equal to 4% of the DXR levels in the tissues; it was, however, a major circulatory metabolite, attaining levels in the plasma as high as 85% of the concentration of DXR.
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