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  • Title: Studies on the comparative distribution and biliary excretion of doxorubicin and 4'-epi-doxorubicin in mice and rats.
    Author: Broggini M, Colombo T, Martini A, Donelli MG.
    Journal: Cancer Treat Rep; 1980; 64(8-9):897-904. PubMed ID: 6934850.
    Abstract:
    Serum and tissue distribution of doxorubicin (DX) and its stereoisomer, 4'-epidoxorubicin (4'-epiDX), after iv injection of 15 mg/kg was investigated in C57BL mice bearing 14-day intramuscular Lewis lung carcinoma. Total fluorescence was measured together with unchanged drugs, separated, and quantitated by means of thin-layer chromatography combined with a scanning fluorescence technique. In serum the disappearance of 4'-epiDX paralleled that of DX and both unchanged isomers represented < 50% of the total fluorescence measured as early as 30 minutes after drug injection. In tissues the fluorescence measured was almost completely accounted for by the native compounds, both DX and 4'-epiDX, indicating that these drugs are taken up as such by tissues. 4'-EpiDX levels were markedly lower than those of DX in tumor and spleen, whereas in heart, liver, and kidneys the concentrations of the two isomers were the same. Traces of doxorubicinol and possibly 4'-epidoxorubicinol were detected only in serum, liver, and kidneys. Comparative cumulative biliary excretion of DX and 4'-epiDX investigated in the rat indicated that a total of 40%-45% of the injected dose of both drugs was excreted either as unchanged compound or as reduced metabolite. However, the proportions were different and the presence of twice as much reduced metabolite and smaller amounts of native 4'-epiDX suggests that its metabolic rate is different from that of DX
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