Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride.

Article Details

Citation

Tani N, Yabuki M, Komuro S, Kanamaru H

Characterization of the enzymes involved in the in vitro metabolism of amrubicin hydrochloride.

Xenobiotica. 2005 Dec;35(12):1121-33. doi: 10.1080/00498250500342746 .

PubMed ID
16418065 [ View in PubMed
]
Abstract

The in vitro metabolism of amrubicin by rat and human liver microsomes and cytosol was examined. The main metabolic routes in both species were reductive deglycosylation and carbonyl group reduction in the side-chain. In vitro metabolism of amrubicinol by rat and human liver microsomes and cytosol was also examined and the main metabolic route of this active metabolite was reductive deglycosylation. Metabolism of amrubicin in human liver microsomes was inhibited by TlCl(3) and that in human liver cytosol was inhibited by dicumarol and quercetin. Generation of amrubicinol was inhibited only by quercetin. The results indicate that metabolism of amrubicin is mediated by NADPH-cytochrome P450 reductase, NADPH:quinone oxidoreductase and carbonyl reductase. In addition, generation of amrubicinol is mediated by carbonyl reductase. Metabolism of amrubicinol in human liver microsomes was inhibited by TlCl(3) and that in human liver cytosol was inhibited by dicumarol. The results indicate that metabolism of amrubicinol is mediated by NADPH-cytochrome P450 reductase and NADPH:quinone oxidoreductase. To investigate the influence of cisplatin on the metabolism of amrubicin and amrubicinol, human liver microsomes and cytosol were pre-incubated with cisplatin. This did not change the rates of amrubicin and amrubicinol metabolism in either human liver microsomes or cytosol.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
AmrubicinCarbonyl reductase [NADPH] 1ProteinHumans
Unknown
Substrate
Details
AmrubicinNADPH--cytochrome P450 reductaseProteinHumans
Unknown
Substrate
Details
Drug Reactions
Reaction
Details
Details