Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/14358
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Type: Journal article
Title: Oxidative metabolism of tamoxifen to Z-4-hydroxy-tamoxifen by cytochrome P450 isoforms: An appraisal of in vitro studies
Author: Coller, J.
Citation: Clinical and Experimental Pharmacology and Physiology, 2003; 30(11):845-848
Publisher: Blackwell Science Asia
Issue Date: 2003
ISSN: 0305-1870
1440-1681
Abstract: 1. Tamoxifen is used for the prevention and treatment of oestrogen receptor-positive breast cancer. 2. Tamoxifen is metabolized extensively and the formation of Z-4-hydroxy-tamoxifen (Z-4-OH-tam), a potent anti-oestrogen with high affinity for the oestrogen receptor, is believed to be strongly related to the therapeutic benefit achieved following tamoxifen treatment. 3. In vitro studies using human liver microsome preparations have shown considerable interindividual variability in the formation rates of Z-4-OH-tam. 4. Cytochrome P450 (CYP) isoform-specific chemical and monoclonal antibody inhibition studies have demonstrated that CYP2B6, CYP2C9, CYP2D6 and CYP3A4 all mediate the formation of Z-4-OH-tam. 5. Significant associations between the percentage inhibition of Z-4-OH-tam by CYP isoform-specific inhibitors and the rate of metabolism of CYP isoform-specific index reactions and between individual expression of CYP2B6, CYP2C9 and CYP2D6 and Z-4-OH-tam formation rates indicate predominant roles for these isoforms in this pathway. 6. Genotyping of patients with regards to CYP2B6, CYP2C9 and CYP2D6 may play a role in prediction of Z-4-OH-tam formation and, consequently, ultimate therapeutic benefit of tamoxifen treatment.
Keywords: Animals; Humans; Breast Neoplasms; Tamoxifen; Cytochrome P-450 Enzyme System; Isoenzymes; Oxidation-Reduction; Polymorphism, Genetic
Description: The definitive version is available at www.blackwell-synergy.com
RMID: 0020031020
DOI: 10.1046/j.1440-1681.2003.03921.x
Published version: http://www.blackwell-synergy.com/doi/full/10.1046/j.1440-1681.2003.03921.x
Appears in Collections:Pharmacology publications

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