TitleThe role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines.
Publication TypeJournal Article
Year of Publication2006
AuthorsKrueger SK, VanDyke JE, Williams DE, Hines RN
JournalDrug Metab Rev
Date Published2006
KeywordsAmines, Animals, Anticarcinogenic Agents, Biotransformation, FMN Reductase, Humans, Tamoxifen

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.

Alternate JournalDrug Metab. Rev.
PubMed ID16684653
Grant ListR01 HL038650 / HL / NHLBI NIH HHS / United States
CA053106 / CA / NCI NIH HHS / United States
HL038650 / HL / NHLBI NIH HHS / United States