Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/14320
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Large interindividual variability in the in vitro formation of tamoxifen metabolites related to the development of genotoxicity |
Author: | Coller, J. Krebsfaenger, N. Klein, K. Wolbold, R. Nussler, A. Neuhaus, P. Zanger, U. Eichelbaum, M. Murdter, T. |
Citation: | British Journal of Clinical Pharmacology, 2004; 57(1):105-111 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2004 |
ISSN: | 0306-5251 1365-2125 |
Statement of Responsibility: | Janet K. Coller, Niels Krebsfaenger, Kathrin Klein, Renzo Wolbold, Andreas Nüssler, Peter Neuhaus, Ulrich M. Zanger, Michel Eichelbaum and Thomas E. Mürdter |
Abstract: | AIMS: To characterize the interindividual variability and the individual CYP involved in the formation of α-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen from tamoxifen. METHODS: Microsomes from 50 human livers were used to characterize the interindividual variability in the α-hydroxylation, N-desmethylation and N-didesmethylation of tamoxifen. Selective inhibitors and recombinant enzymes were used to identify the forms of CYP catalysing these reactions. RESULTS: The rates of formation of α-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen were highly variable, and correlated with each other (P < 0.0001). The respective ranges were 0.7–11.4, 25.7–411, and below the limit of quantification – 4.4 pmol mg1 protein min1. Formation of all metabolites was observed with expressed recombinant CYP3A4, inhibited by troleandomycin (65, 77 and 35%, respectively, P < 0.05) and associated with CYP3A4 expression (rs = 0.612, rs = 0.585 and rs = 0.430, P < 0.01, respectively). CONCLUSIONS: Formation of α-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen in vitro is highly variable and mediated predominantly by CYP3A4. |
Keywords: | Microsomes, Liver Humans Tamoxifen Cytochrome P-450 Enzyme System Adolescent Adult Aged Middle Aged Child Child, Preschool Female Male Cytochrome P-450 CYP3A Genetic Variation |
Description: | The definitive version is available at www.blackwell-synergy.com |
DOI: | 10.1046/j.1365-2125.2003.01970.x |
Published version: | http://www.blackwell-synergy.com/doi/full/10.1046/j.1365-2125.2003.01970.x |
Appears in Collections: | Aurora harvest 7 Pharmacology publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.