Artigo

CYP3A4*22 is related to increased plasma levels of 4-hydroxytamoxifen and partially compensates for reduced CYP2D6 activation of tamoxifen

Marina Venzon Antunes, Vanessa de Oliveira, Suziane Raymundo, Dilana Elisabeth Staudt, Gustavo Goessling, JORGE VILLANOVA BIAZUS, José Antônio Cavalheiro, DANIELA DORNELLES ROSA, Geneviève Mathy, Pierre Wallemacq, Rafael Linden, Gilberto Schwartsmann, Vincent Haufroid

Pharmacogenomics, v. 16, n. 6, p. 601-617, 2015.

Motivo: Produção Colaborador HMV

Setor HMV: Farmacia Clinica/Dispensacao

Área da saúde: Farmácia, Farmácia - Farmácia

Resumo: Aim: To evaluate the impact of CYP3A4*22 in the formation of endoxifen (EDF) and hydroxytamoxifen (HTF), under different CYP2D6 genotypic backgrounds. Materials & methods: 178 patients were enrolled in the study. CYP2D6 and CYP3A4 genotyping and tamoxifen (TAM) and metabolites quantification were performed. Results: 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). Conclusion: 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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