Fig. 2. Metabolic activation of tamoxifen. Phase I metabolism of tamoxifen produces phenolic metabolites that have a high bindingaffinity for the ER and thus exerts potent antiestrogenic activity. Metabolic pathways mainly include cytochrome P450 3A4/5 and 2D6. Further oxidative metabolism may contribute to formation of reactive intermediates such as quinone methides. The thickness of each arrow indicates the relative contribution of the respective pathway to the formation of a specific metabolite. The principal metabolizingenzymes responsible for biotransformation are indicated next to the arrow.
