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106 5 Multi-Enzyme Systems and Cascade Reactions Involving Cytochrome P450 Monooxygenases
O
N
Tamoxifen
N-demethylation Hydroxylation
CYPs 3A4/3A5 CYP2D6 Primary metabolism
O O
N N
H
4
OH
N-Desmethyltamoxifen 4-Hydroxytamoxifen
Hydroxylation N-demethylation Hydroxylation N-demethylation Hydroxylation
CYP3A CYP3A CYP2D6 CYP3A CYP3A
O O O O
N NH 2 N N
H H Secondary metabolism
OH 3 OH
4 4
OH OH
α-Hydroxy-N-desmethyltamoxifen N-Didesmethyltamoxifen 4-Hydroxy-N-desmethyltamoxifen 3,4-Dihydroxytamoxifen
(Endoxifen)
Scheme 5.17 Metabolism of tamoxifen by N-demethylations and hydroxylations. Bold arrows and enzymes indicate major
routes of tamoxifen metabolism.
