Get to know Tamoxifen
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Tamoxifen metabolism is complex and not completely understood. Tamoxifen is a nonsteroidal selective estrogen receptor modulator (SERM) hormone therapy used in breast cancer that strongly inhibits the effects of estrogen in breast tissue. Tamoxifen is a prodrug that is metabolized by several cytochrome P450 enzymes in phase I detoxification. CYP2B6, CYP2C8, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 transform tamoxifen into both active and inactive metabolites. For many years, 4-hydroxy-tamoxifen has believed to be primarily responsible for the clinical activity; however, the CYP2D6 metabolites 4-hydroxy-tamoxifen and endoxifen have equal affinity for the estrogen receptor. Because serum concentrations of endoxifen are 6 to 12 times higher than 4-hydroxy-tamoxifen in patients receiving long-term tamoxifen therapy, many think endoxifen is the most significant tamoxifen metabolite.