Cytochrome P-450 3A and 2D6 catalyze ortho hydroxylation of 4-hydroxytamoxifen and 3-hydroxytamoxifen (droloxifene) yielding tamoxifen catechol: involvement of catechols in covalent binding to hepatic proteins

UMMS Affiliation

Worcester Foundation for Biomedical Research; Department of Pharmacology and Molecular Toxicology

Publication Date


Document Type



Animals; Biotransformation; Catechols; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; Estrogen Antagonists; Humans; Hydroxylation; Liver; Mixed Function Oxygenases; Pentobarbital; Protein Binding; Rats; Rats, Sprague-Dawley; Tamoxifen


Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences | Pharmacology, Toxicology and Environmental Health


Earlier study suggested that 3,4-dihydroxytamoxifen (tam catechol), a tamoxifen metabolite, is proximate to the reactive intermediate that binds covalently to proteins and possibly to DNA (). The current study demonstrates that rat and human hepatic cytochrome P-450s (CYPs) catalyze tam catechol formation from tamoxifen (tam), 3-hydroxy-tam (Droloxifene), and 4-hydroxy-tam (4-OH-tam). Higher levels of catechol were formed from 4-OH-tam and 3-hydroxy-tam than from tam. Evidence that human hepatic CYP3A4 and 2D6 catalyze the formation of tam catechol from 4-OH-tam and supportive data that the catechol is proximate to the reactive intermediate, was obtained: 1) There was a good correlation (r = 0.82; p


Drug Metab Dispos. 1999 Jun;27(6):681-8.

Journal/Book/Conference Title

Drug metabolism and disposition: the biological fate of chemicals

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Link to Article in PubMed

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