What is the Origin of Endoxifen Metabolism?

This term is a cornerstone of clinical pharmacology and pharmacogenetics, specifically within the context of anti-estrogen therapy. The identification of endoxifen as the major active metabolite, rather than the parent drug tamoxifen, established the importance of individual metabolic capacity in treatment outcomes. This understanding led to the clinical utility of genotyping specific metabolic enzymes.

What is the Mechanism of Endoxifen Metabolism?

The biotransformation is predominantly mediated by the cytochrome P450 2D6 (CYP2D6) enzyme, which catalyzes the 2-hydroxylation of tamoxifen into N-desmethyltamoxifen, which is then further metabolized into endoxifen. Genetic polymorphisms in the CYP2D6 gene directly influence enzyme activity, classifying individuals as poor, intermediate, or ultrarapid metabolizers. These genetic variations result in significant inter-patient variability in endoxifen plasma concentrations, thereby necessitating genotype-guided dosing strategies for optimal therapeutic effect.

Endoxifen Metabolism ∞ Area

Endoxifen Metabolism

Meaning

Endoxifen metabolism refers to the specific biochemical pathways responsible for the enzymatic conversion of tamoxifen, a selective estrogen receptor modulator (SERM), into its highly potent active metabolite, endoxifen. This conversion is a crucial determinant of tamoxifen’s therapeutic efficacy in the treatment of estrogen receptor-positive breast cancer. The circulating concentration of endoxifen is directly correlated with clinical response, making its metabolic pathway a focus of personalized medicine.