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

Pharmacogenomics

Volumn 16, Issue 6, 2015, Pages 601-617

  Antunes, Marina Venzon ^a,b   De Oliveira, Vanessa ^b   Raymundo, Suziane ^b   Staudt, Dilana Elisabeth ^b   Gössling, Gustavo ^c   Biazús, Jorge Villanova ^c   Cavalheiro, José Antônio ^c   Rosa, Daniela Dornelles ^d   Mathy, Geneviève ^e   Wallemacq, Pierre ^e   Linden, Rafael ^b   Schwartsmann, Gilberto ^a,c   Haufroid, Vincent ^e  

^a FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^b UNIVERSIDADE FEEVALE   (Brazil)

^c HOSPITAL DE CLÍNICAS DE PORTO ALEGRE   (Brazil)

^d HOSPITAL MOINHOS DE VENTO   (Brazil)

^e UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

Author keywords

4 hydroxytamoxifen; CYP2D6; CYP3A4; endoxifen; genotype; tamoxifen

Indexed keywords

AFIMOXIFENE; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; ENDOXIFEN; TAMOXIFEN; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A;

ADULT; AGED; ALOPECIA; ARTICLE; CYP2D6 GENE; CYP3A4 GENE; DIZZINESS; DRUG BLOOD LEVEL; DRUG METABOLISM; DRUG STRUCTURE; FEMALE; GENE FREQUENCY; GENOTYPE; HOT FLUSH; HUMAN; MAJOR CLINICAL STUDY; MEDICATION COMPLIANCE; NAUSEA; PATIENT COMPLIANCE; PHARMACOGENETICS; RASH; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOSIS; VAGINA BLEEDING; VAGINA DISCHARGE; VOMITING; VULVA PRURITUS; ANALOGS AND DERIVATIVES; BLOOD; ENZYME ACTIVATION; GENETICS; MALE; MIDDLE AGED; PHYSIOLOGY; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; ENZYME ACTIVATION; FEMALE; HUMANS; MALE; MIDDLE AGED; TAMOXIFEN;

EID: 84929452976     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.15.13     Document Type: Article

References (25)

1. Brauch H, Murdter TE, Eichelbaum M, Schwab M. Pharmacogenomics of tamoxifen therapy. Clin. Chem. 55, 1770-1782 (2009).
2. Jung JA, Lim HS. Association between CYP2D6 genotypes and the clinical outocomes of adjuvant tamoxifen for breast cancer: a meta-analysis. Pharmacogenomics 15(1), 49-60 (2014).
3. Jordan VC, Collins MM, Rowsby L, Prestwich G. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J. Endocrinol. 75, 305-316 (1977).
4. Teunissen SF, Rosing H, Koornstra RHT et al. Development and validation of a quantitative assay for the analysis of tamoxifen with its four main metabolites and flavonoids daidzein, genistein and glycitein in human serum using liquid chromatography coupled with tandem mass spectrometry. J. Chromatogr. B. 877, 2519-2529 (2009).
5. Mürdter TE, Schroth W, Bacchus-Gerybadze L et al. Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma. Clin. Pharmacol. Ther. 89, 708-717 (2011).
6. Ahsen NV, Binder C, Brosckmoller J, Oellerich M. CYP2D6 and tamoxifen: pharmacogenetic reinvention of an established drug? J. Lab. Med. 33(5), 1-9 (2009).
7. Madlensky L, Natarajan L, Tchu T et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin. Pharm. Therap. 89(5), 718-725 (2011).
8. Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin. Pharmacol. Ter. 83, 234-242 (2008).
9. Borges S, Desta Z, Jin Y et al. Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patients. J. Clin. Pharmacol. 50, 450-458 (2010).
10. Teh LK, Bertilsson L. Pharmacogenomics of CYP2D6: Molecular genetics, interethnic differences and clinical importance. Drug Metab. Pharmacokinet. 17(1), 55-67 (2012).
11. Kohlrausch FB, Gama CS, Lobato MI et al. Molecular diversity at the CYP2D6 locus in healthy and schizophrenic souther Brazilians. Pharmacogenomics 10(9), 1457-1466 (2009).
12. Friedrich DC, Genro JP, Sortica VA et al. Distribution of CYP2D6 alleles and phenotypes in the Brazilian population. PLoS ONE 9(10), e110691 (2014).
13. Antunes MV, Linden R, Santos TV et al. Endoxifen levels and its association With CYP2D6 genotype and phenotype: evaluation of a southern Brazilian population under tamoxifen pharmacotherapy. Ther. Drug Monit. 34, 422-431 (2012).
14. Irvin WJ, Walko CM, Weck KE et al. Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study. J. Clin. Oncol. 29(24), 3232-3239 (2011).
15. Musshoff F, Stamer UM, Madea B. Pharmacogenetics and forensic toxicology. Forensic Sci. Int. 203, 53-62 (2010).
16. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J. Steroid Biochem. 136, 54-58 (2013).
17. Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J. 11, 274-286 (2011).
18. Teft WA, Gong IY, Dingle B et al. CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy. Breast Cancer Res. Treat. 139, 95-105 (2013).
19. Heine R, Binkhorst L, de Graan AJM. Population pharmacokinetic modelling to assess the impact of CYP2D6 and CYP3A metabolic phenotypes on the pharmacokinetics of tamoxifen and endoxifen. Br. J. Clin. Pharmacol. 78(3), 572-586 (2014).
20. Elens L, van Schaik RH, Panin N et al. Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors' dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics 12, 1383-1396 (2011).
21. Antunes MV, Raymundo S, Oliveira V et al. Ultra-high performance liquid chromatography tandem mass spectrometric method for the determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots-development, validation and clinical application during breast cancer adjuvant therapy. Talanta 132, 775-784 (2015).
22. Bijl MJ, van Schaik RHN, Lammers LA et al. The CYP2D6∗4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Res. Treat. 118(1), 125-130 (2009).
23. Schroth W, Goetz M, Hamma U et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302(13), 1429-1436 (2009).
24. Jager NGL, Rosing H, Schellens JHM, Linn SC, Beijnen JH. Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care. Breast Cancer Res. Treat. 143, 477-483 (2014).
25. Heath DD, Flat SW, Wu AH, Pruitt MA, Rock CL. Evaluation of tamoxifen and metabolites by LC-MS/MS and HPLC methods. Br. J. Biomed. Sci. 71, 33-39 (2014).