Mitoxantrone metabolism in the isolated perfused rat liver

The hepatobiliary pharmacokinetics of mitoxantrone, a new anthracenedione derivative, was studied in the isolated perfused rat liver. Mitoxantrone was administered in doses of 0.2 and 0.4 mg/kg body weight. Multiple bile samples were obtained for 4 hours. Mitoxantrone and three metabolites were sepa...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1984, Vol.12 (1), p.50-52
Main Authors: EHNINGER, G, PROKSCH, B, HARTMANN, F, GARTNER, H.-V, WILMS, K
Format: Article
Language:English
Subjects:
Animals
Anthraquinones - metabolism
Antineoplastic agents
Bile - metabolism
Biological and medical sciences
Chromatography, High Pressure Liquid
General aspects
Liver - metabolism
Male
Medical sciences
Mitoxantrone
Perfusion
Pharmacology. Drug treatments
Rats
Rats, Inbred Strains
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Summary:The hepatobiliary pharmacokinetics of mitoxantrone, a new anthracenedione derivative, was studied in the isolated perfused rat liver. Mitoxantrone was administered in doses of 0.2 and 0.4 mg/kg body weight. Multiple bile samples were obtained for 4 hours. Mitoxantrone and three metabolites were separated by high-performance thin-layer chromatography (HPTLC) and measured at 610 nm. Following 0.2 mg mitoxantrone/kg body wt, 25.8% +/- 2.6% of the administered dose was excreted in the bile during 4 h, the major metabolite M1 accounting for 80% of this. After 0.4 mg mitoxantrone/kg body wt the amounts excreted were lower and light microscopic examination showed disseminated areas of cell necrosis.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00255910