Comparing the concentration of tamoxifen and its metabolites between different genotypes of CYP2D6 gene

Tamoxifen has been extensively used for adjuvant endocrine therapy of ER-positive breast cancer patients. Tamoxifen acts as a prodrug that its effects are due to its active metabolites. Some of these metabolites have more anti-estrogenic effects in breast cancer tissue than tamoxifen, itself. The metabolism of tamoxifen is accomplished through two pathways called 4-Hydroxylation and N-desmethylation. CytochromeP450 2D6 (CYP2D6) is an important drug metabolizing enzyme involved in the pharmacokinetic metabolism of tamoxifen. Since the response of each person to tamoxifen is different from that of the human pharmacodynamics agent in tamoxifen metabolism, in the current study, for the first time in Iranian population, the concentration of tamoxifen and its metabolites in individuals with different CYP2D6 genotypes were compared.The concentration of tamoxifen and its metabolites were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 134 breast cancer patient from Isfahan province of Iran. Then, the differences of the tamoxifen and its metabolites between different genotypes were evaluated using Kruskal-Wallis test. Steady-state plasma concentrations of tamoxifen and its metabolites was measured using LC-MS/MS technique. In addition to (Z) and (E)-endoxifen concentration, as the most important metabolites of tamoxifen, the concentration of some other metabolites were also showed significant differences between different genotypic groups.Taken together, our data demonstrated the relationship between CYP2D6 genotypes and plasma concentrations of tamoxifen and its metabolites; therefore it s important to detect these patients to prevent adverse drug reactions through individualization therapy.

Keywords:

concentration , CYP2D6 , endoxifen , metabolites , tamoxifen