The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines.
Article Details
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Krueger SK, Vandyke JE, Williams DE, Hines RN
The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines.
Drug Metab Rev. 2006;38(1-2):139-47.
- PubMed ID
- 16684653 [ View in PubMed]
- Abstract
Tamoxifen is utilized in breast cancer therapy and in chemoprevention. Tamoxifen may enhance risk for other neoplasias, especially endometrial cancer. The risk:benefit depends on the rate of metabolic activation versus detoxication. Cytochrome P450-dependent alpha-hydroxylation, followed by sulfonation, represents a metabolic activation pathway, producing products capable of covalent DNA adduction. In contrast, tamoxifen N-oxygenation represents a detoxication pathway, with the caveat that N-oxides can be reduced back to the parent amines. The N-oxygenation pathway will be the focus for this review. Dr. David Kupfer pioneered studies on cytochrome P450 and flavin-containing monooxygenase (FMO) tamoxifen metabolism. We collaborated with Dr. Kupfer's laboratory and recently determined that the low level of tamoxifen N-oxide production in human liver microsomes may be explained by the kinetics of FMO1 versus FMO3.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Tamoxifen Dimethylaniline monooxygenase [N-oxide-forming] 1 Protein Humans UnknownSubstrateDetails Tamoxifen Dimethylaniline monooxygenase [N-oxide-forming] 3 Protein Humans UnknownSubstrateDetails