Beverage Jacob N, Sissung Tristan M, Sion Amy M, Danesi Romano, Figg William D
Clinical Pharmacology Research Core, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, Maryland, USA.
J Pharm Sci. 2007 Sep;96(9):2224-31. doi: 10.1002/jps.20892.
The cytochrome P450 2D6 (CYP2D6) is an enzyme known to metabolize a variety of xenobiotics and drugs. Inter-individual variation in the metabolic capacity of this enzyme has been extensively studied and associations with genotype have been established. Genetic polymorphisms have been grouped as nonfunctional, reduced function, functional, and multiplication alleles phenotypically. Individuals carrying these alleles are presumed to correspond to poor, intermediate, extensive, and ultrarapid metabolizers (UM), respectively. Tamoxifen has been shown to be metabolized by CYP2D6 to the more potent metabolite endoxifen. Poor metabolizers (PM) of tamoxifen have lower levels of endoxifen and poorer clinical outcomes as compared to extensive metabolizers (EM). Here, we will provide an overview of the history and application of CYP2D6 pharmacogenetics, and will discuss the clinical implications of recent developments relating to the involvement of CYP2D6 in tamoxifen treatment.
细胞色素P450 2D6（CYP2D6）是一种已知可代谢多种外源性物质和药物的酶。该酶代谢能力的个体间差异已得到广泛研究，并已建立了与基因型的关联。遗传多态性在表型上已被分为无功能、功能降低、功能正常和倍增等位基因。携带这些等位基因的个体分别被认为对应于代谢不良者、中间代谢者、代谢广泛者和超快代谢者（UM）。他莫昔芬已被证明可被CYP2D6代谢为活性更强的代谢产物endoxifen。与代谢广泛者（EM）相比，他莫昔芬代谢不良者（PM）的endoxifen水平较低，临床结局较差。在此，我们将概述CYP2D6药物遗传学的历史和应用，并将讨论与CYP2D6参与他莫昔芬治疗相关的最新进展的临床意义。
