Scopus Publication Detail
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Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age
Z. Desta; Y. Kreutz; A.T. Nguyen; L. Li; T. Skaar; L.K. Kamdem; N.L. Henry; D.F. Hayes; A.M. Storniolo; V. Stearns; et al. (Profiled Authors: Lang Li; Zeruesenay Desta; David A. Flockhart; Todd C. Skaar; Anna Maria V. Storniolo)
Clinical Pharmacology and Therapeutics. 2011;90(5):693-700.Abstract
The associations between plasma letrozole concentrations and CYP2A6 and CYP3A5 genetic variants were tested in the Exemestane and Letrozole Pharmacogenomics (ELPH) trial. ELPH is a multicenter, open-label prospective clinical trial in women randomly assigned (n 250 in each arm) to receive 2 years of treatment with either oral letrozole (2.5 mg/day) or oral exemestane (25 mg/day). CYP2A6 and CYP3A showed effects on letrozole metabolism in vitro. DNA samples were genotyped for variants in the CYP2A6 and CYP3A5 genes. Plasma letrozole concentrations showed high interpatient variability (10-fold) and were associated significantly with CYP2A6 genotypes (P 0.0001), body mass index (BMI) (P 0.0001), and age (P = 0.0035). However, CYP3A5 genotypes showed no association with plasma letrozole concentrations. These data suggest that CYP2A6 is the principal clearance mechanism for letrozole in vivo. CYP2A6 metabolic status, along with BMI and age, may serve as a biomarker of the efficacy of letrozole treatment or a predictor of adverse effects. © 2011 American Society for Clinical Pharmacology and Therapeutics.
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