Is tamoxifen metabolized by CYP2D6?

Is tamoxifen metabolized by CYP2D6?

Tamoxifen is metabolized via CYP2D6 into endoxifen (4-OH-N-desmethyl-tamoxifen), its primary active metabolite. Multiple investigations have identified genetic variants of CYP2D6 that can affect its activity, which in turn affects the metabolism of tamoxifen.

Is tamoxifen metabolized by cyp450?

Tamoxifen is a pro-drug that is metabolised to its active metabolites by the cytochrome P450 (CYP) enzymes including CYP2D6, CYP3A, CYP2B6, and CYP2C19. The CYP genes are polymorphic resulting in variable enzyme activity.

Is tamoxifen a competitive inhibitor?

Tamoxifen, an antiestrogen, is a competitive inhibitor of estradiol, blocking its effects on the target organs. During the 10 years it has been used in the United States it has become preferred over estrogens for treating postmenopausal women with metastatic breast cancer.

Where is tamoxifen metabolized?

Tamoxifen is extensively metabolized predominantly by the cytochrome P450 (CYP) system into several primary and secondary metabolites, some of which exhibit more antiestrogenic effects in breast cancer cells than tamoxifen itself [2,22,23].

What enzymes metabolize tamoxifen?

Tamoxifen is metabolized to more active forms by various cytochrome P450 enzymes (CYP2D6, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) (Figure 1) [7–11]. Each metabolite has its own specific binding affinity for the ER [12].

What CYP is warfarin?

Warfarin is a racemic mixture of its R-isomer (less potent) and S-isomer (more potent). S-warfarin is metabolized primarily by the CYP 2C9 isoenzyme whereas R-warfarin is metabolized by CYP 1A2 and 3A4.

Is tamoxifen a prodrug?

Tamoxifen is widely prescribed to patients with estrogen receptor-positive breast cancer, and it is a prodrug that requires bioactivation by cytochrome P450 enzymes CYP2D6 and 3A4 to generate the active metabolite, endoxifen.