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The metabolism and disposition of marcellomycin (MCM), a new anthracycline antitumor antibiotic, were studied after iv administration to mice. In plasma, total drug fluroescence decreased according to first order kinetics and was mainly comprised of parent drug. In addition to MCM, five compounds (M2, P1, P2, G1, G2) were seen. M2 reflected the presence of(More)
Rat liver microsomes under anaerobic conditions metabolize adriamycin (ADM) to 7-deoxyadriamycinol aglycone and 7-deoxyadriamycin aglycone. The metabolism of ADM and the concentration of cytochrome P-450 were not affected by preincubation with 2.76 mM cyclophosphamide. After preincubation of microsomes with 0.2 mM 4-hydroperoxycyclophosphamide, a prodrug of(More)
In conjunction with two phase I clinical trials, we have investigated the pharmacokinetics of marcellomycin (MCM), a new class II anthracycline antibiotic, in nine patients with normal renal and hepatic functions and no third-space fluid accumulation. MCM was infused IV over 15 min at a dosage of 27.5, 40, or 50 mg/m2. Plasma and urine samples were(More)
The in vitro metabolism of marcellomycin by rat tissue fractions showed conversion of marcellomycin to 7-deoxypyrromycinone, bisanhydropyrromycinone, and an as yet unidentified compound by rat liver homogenate, microsomes, cytosol, and mitochondria, and purified hepatic reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, under(More)
The metabolism and tissue distribution of aclacinomycin A (ACL), marcellomycin (MCM), and musettamycin (MST), three new anthracycline antibiotics, were compared after IV administration to mice. In plasma, total MCM- and ACL-derived fluorescence declined according to first-order kinetics, whereas an initial decline followed by a rebound was observed for MST.(More)
Under anaerobic conditions, in comparison to liver microsomes obtained from normal controls, liver microsomes obtained from rats pretreated with cyclophosphamide formed significantly less 7-deoxydoxorubicinol aglycone (P less than or equal to .05), whereas the disappearance of doxorubicin and the formation of 7-deoxydoxorubicin aglycone were unaffected.(More)
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