Simplified biotransformation scheme of tamoxifen in man. Tamoxifen is mainly N-demethylated to NDM-TAM and subsequently 4-hydroxylated to endoxifen. A minor pathway proceeds via 4-hydroxylation to 4OH-TAM followed by N-demethylation to endoxifen. The polymorphic CYP2D6 is involved in crucial steps of the endoxifen formation. Abbreviations used in diagram: cytochrome P450 (CYP), sulfonyltransferase (SULT), uridine-5′-diphosphoglucuronyltransferase (UGT), tamoxifen (TAM), N-desmethyltamoxifen (NDM), 4-hydroxytamoxifen (4OH), endoxifen (END).