CYP3A4*22is related to increased plasma levels of 4-hydroxytamoxifen and partially compensates for reduced CYP2D6 activation of tamoxifen
(2015) Pharmacogenomics — Vol. 16, n° 6, p. 601-617 (2015)
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- (en) 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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Antunes, M. V., de Oliveira, V., Raymundo, S., Staudt, D. E., Gössling, G., Biazús, J. V., Cavalheiro, J. A., Rosa, D. D., Mathy, G., Wallemacq, P., Linden, R., Schwartsmann, G., & Haufroid, V. (2015). CYP3A4*22is related to increased plasma levels of 4-hydroxytamoxifen and partially compensates for reduced CYP2D6 activation of tamoxifen. Pharmacogenomics, 16(6), 601-617. https://doi.org/10.2217/PGS.15.13 (Original work published 2015)