AI Article Synopsis
- The study assessed how the CYP3A4*22 variant affects the production of endoxifen (EDF) and hydroxytamoxifen (HTF) in different CYP2D6 genetic backgrounds among 178 patients.
- EDF levels were found to be significantly lower in poor and intermediate CYP2D6 metabolizers compared to those with normal metabolism, but CYP3A4*22 carriers had significantly higher HTF and TAM levels.
- The results suggest that CYP3A4*22 may help offset the reduced EDF levels due to CYP2D6 inactivity, particularly by boosting HTF concentrations.
Article Abstract
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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| http://dx.doi.org/10.2217/pgs.15.13 | DOI Listing |
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