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Debrisoquine Metabolism and CYP2D Expression in Marmoset Liver Microsomes.

Cooke, BR, Bligh, SW, Cybulski, ZR, Ioannides, C and Hall, M (2011) Debrisoquine Metabolism and CYP2D Expression in Marmoset Liver Microsomes. Drug Metab Dispos.

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Abstract

The objective of this study was to define CYP2D enzymes in marmoset (Callithrix jacchus) liver microsomes, both at the activity level using debrisoquine as the model substrate, and at the protein level employing antibodies raised to human CYP2D6. Marmoset liver microsomes were incubated with [(14)C]debrisoquine and the structure of the generated metabolites determined using liquid chromatography-tandem mass spectrometry and NMR. Marmoset liver microsomes were very effective in hydroxylating debrisoquine at various positions. Although 4-hydroxydebrsoquine was formed, in contrast to rat and human it was only a minor metabolite. Debrisoquine was more extensively hydroxylated in the 7-, 5-, 6- and 8-positions. In addition to the mono-hydroxylated metabolites, a dihydroxy metabolite, namely 6,7-dihydroxydebrisoquine was identified. Finally, metabolites that had undergone ring-opening were also detected but were not investigated further. Antibodies to CYP2D6 immunoreacted with protein in marmoset and human, but not rat hepatic microsomes. In conclusion, we have demonstrated that marmoset liver microsomes are effective in hydroxylating debrisoquine at various positions and that they contain a protein that is immunorelated to human CYP2D6.

Item Type: Article
Authors :
NameEmailORCID
Cooke, BRUNSPECIFIEDUNSPECIFIED
Bligh, SWUNSPECIFIEDUNSPECIFIED
Cybulski, ZRUNSPECIFIEDUNSPECIFIED
Ioannides, CUNSPECIFIEDUNSPECIFIED
Hall, MUNSPECIFIEDUNSPECIFIED
Date : 5 October 2011
Identification Number : 10.1124/dmd.111.041566
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 14:41
Last Modified : 31 Oct 2017 14:29
URI: http://epubs.surrey.ac.uk/id/eprint/294622

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