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CYP3A422 is Related to Increased Plasma Levels of 4-Hydroxytamoxifen and Partially Compensates for Reduced CYP2D6 Activation of Tamoxifen

by Staudt, Dilana Elisabeth , Wallemacq, Pierre , Biazús, Jorge Villanova , Schwartsmann, Gilberto , Gössling, Gustavo , Mathy, Geneviève , Linden, Rafael , Cavalheiro, José Antônio , Haufroid, Vincent , de Oliveira, Vanessa , Raymundo, Suziane , Rosa, Daniela Dornelles , Antunes, Marina Venzon

in Adult / Aged / Aged, 80 and over / Blood plasma / Cytochrome P-450 / Cytochrome P-450 CYP2D6 - genetics / Cytochrome P-450 CYP3A - genetics / Drug metabolism / Enzyme Activation - physiology / Female / Genetic aspects / Health aspects / Humans / Male / Middle Aged / Patient outcomes / Properties / Tamoxifen / Tamoxifen - analogs & derivatives / Tamoxifen - blood

2015

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CYP3A422 is Related to Increased Plasma Levels of 4-Hydroxytamoxifen and Partially Compensates for Reduced CYP2D6 Activation of Tamoxifen

2015

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CYP3A422 is Related to Increased Plasma Levels of 4-Hydroxytamoxifen and Partially Compensates for Reduced CYP2D6 Activation of Tamoxifen

2015

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Journal Article

CYP3A422 is Related to Increased Plasma Levels of 4-Hydroxytamoxifen and Partially Compensates for Reduced CYP2D6 Activation of Tamoxifen

Staudt, Dilana Elisabeth,

Wallemacq, Pierre,

Biazús, Jorge Villanova,

Schwartsmann, Gilberto,

Gössling, Gustavo,

Mathy, Geneviève,

Linden, Rafael,

Cavalheiro, José Antônio,

Haufroid, Vincent,

de Oliveira, Vanessa,

Raymundo, Suziane,

Rosa, Daniela Dornelles,

Antunes, Marina Venzon

2015

Overview

To evaluate the impact of CYP3A4*22 in the formation of endoxifen (EDF) and hydroxytamoxifen (HTF), under different CYP2D6 genotypic backgrounds. 178 patients were enrolled in the study. CYP2D6 and CYP3A4 genotyping and tamoxifen (TAM) and metabolites quantification were performed. EDF concentrations were lower in poor (2.77 ng ml(-1)) and CYP2D6 intermediate metabolizers (5.84 ng ml(-1)), comparing to functional group (EM-F) (10.67 ng ml(-1), p < 0.001). HTF and TAM levels were respectively 47 and 53% higher in CYP3A4*22 carriers compared with *1/*1 patients in the whole group. Patients with impaired CYP2D6 metabolism and carriers of CYP3A4*22 had EDF levels comparable to CYP2D6 EM-F group (9.06 and 10.67 ng ml(-1), p = 0.247). The presence of CYP3A4*22 might compensate the reduction of EDF concentrations related to CYP2D6 inactivity, especially due to increased HTF concentrations.

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Publisher

Future Medicine Ltd

Subject

/ Aged

/ Cytochrome P-450 CYP2D6 - genetics

/ Cytochrome P-450 CYP3A - genetics