Abstract | BACKGROUND: METHODS: RESULTS: Among all women, plasma endoxifen concentrations after 4 months of tamoxifen therapy were statistically significantly lower in subjects with a CYP2D6 homozygous variant genotype (20.0 nM, 95% confidence interval [CI] = 11.1 to 28.9 nM) or a heterozygous genotype (43.1 nM, 95% CI = 33.3 to 52.9 nM) than in those with a homozygous wild-type genotype (78.0 nM, 95%CI = 65.9 to 90.1 nM) (both P = .003). Among subjects who carried a homozygous wild-type genotype, the mean plasma endoxifen concentration for those who were using CYP2D6 inhibitors was 58% lower than that for those who were not (38.6 nM versus 91.4 nM, difference = -52.8 nM, 95% CI = -86.1 to -19.5 nM, P = .0025). The plasma endoxifen concentration was slightly reduced in women taking venlafaxine, a weak inhibitor of CYP2D6, whereas the plasma endoxifen concentration was reduced substantially in subjects who took paroxetine (a potent inhibitor of CYP2D6). Genetic variations of CYP2C9, CYP3A5, or SULT1A1 had no statistically significant associations with plasma concentrations of tamoxifen or its metabolites. CONCLUSION:
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Authors | Yan Jin, Zeruesenay Desta, Vered Stearns, Bryan Ward, Herbert Ho, Kyung-Hoon Lee, Todd Skaar, Anna Maria Storniolo, Lang Li, Adjei Araba, Rebecca Blanchard, Anne Nguyen, Lynda Ullmer, Jill Hayden, Suzanne Lemler, Richard M Weinshilboum, James M Rae, Daniel F Hayes, David A Flockhart |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 97
Issue 1
Pg. 30-9
(Jan 05 2005)
ISSN: 1460-2105 [Electronic] United States |
PMID | 15632378
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antidepressive Agents, Second-Generation
- Antineoplastic Agents, Hormonal
- Cyclohexanols
- Cytochrome P-450 CYP2D6 Inhibitors
- Enzyme Inhibitors
- Estrogen Receptor Modulators
- Serotonin Uptake Inhibitors
- Tamoxifen
- Venlafaxine Hydrochloride
- Cytochrome P-450 Enzyme System
- CYP2C9 protein, human
- Cytochrome P-450 CYP2C9
- Aryl Hydrocarbon Hydroxylases
- CYP3A protein, human
- CYP3A5 protein, human
- Cytochrome P-450 CYP2D6
- Cytochrome P-450 CYP3A
- Arylsulfotransferase
- SULT1A1 protein, human
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Topics |
- Adult
- Aged
- Antidepressive Agents, Second-Generation
(administration & dosage, metabolism)
- Antineoplastic Agents, Hormonal
(administration & dosage, blood, metabolism)
- Aryl Hydrocarbon Hydroxylases
(genetics)
- Arylsulfotransferase
(genetics)
- Breast Neoplasms
(drug therapy, enzymology, metabolism)
- Chemotherapy, Adjuvant
- Cyclohexanols
(metabolism)
- Cytochrome P-450 CYP2C9
- Cytochrome P-450 CYP2D6
(genetics)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP3A
- Cytochrome P-450 Enzyme System
(genetics)
- Drug Administration Schedule
- Enzyme Inhibitors
(metabolism)
- Estrogen Receptor Modulators
(administration & dosage, blood, metabolism)
- Female
- Genotype
- Humans
- Middle Aged
- Prospective Studies
- Selective Serotonin Reuptake Inhibitors
(administration & dosage, metabolism)
- Tamoxifen
(administration & dosage, blood, metabolism)
- Time Factors
- Venlafaxine Hydrochloride
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