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 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.
D000818:Animals; D000880:Anthraquinones / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000378:metabolism*; D008297:Male; D008942:Mitoxantrone; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000880:Anthraquinones; D008942:Mitoxantrone