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.
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.
Authors: A B Sanchez Spitman; D J A R Moes; H Gelderblom; V O Dezentje; J J Swen; H J Guchelaar Journal: Eur J Clin Pharmacol Date: 2017-08-28 Impact factor: 2.953
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Authors: Lena Ekström; Ilona Skilving; Marie-Louise Ovesjö; Eleni Aklillu; Hanna Nylén; Anders Rane; Ulf Diczfalusy; Linda Björkhem-Bergman Journal: Pharmacol Res Perspect Date: 2015-10-27
Authors: Tessa A M Mulder; Ruben A G van Eerden; Mirjam de With; Laure Elens; Dennis A Hesselink; Maja Matic; Sander Bins; Ron H J Mathijssen; Ron H N van Schaik Journal: Front Genet Date: 2021-07-08 Impact factor: 4.599