Xie H G, Kim R B, Wood A J, Stein C M
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Annu Rev Pharmacol Toxicol. 2001;41:815-50. doi: 10.1146/annurev.pharmtox.41.1.815.
Ethnicity is an important demographic variable contributing to interindividual variability in drug metabolism and response. In this rapidly expanding research area many genetic factors that account for the effects of ethnicity on pharmacokinetics, pharmacodynamics, and drug safety have been identified. This review focuses on recent developments that have improved understanding of the molecular mechanisms responsible for such interethnic differences. Genetic variations that may provide a molecular basis for ethnic differences in drug metabolizing enzymes (CYP 2C9, 2C19, 2D6, and 3A4), drug transporter (P-glycoprotein), drug receptors (adrenoceptors), and other functionally important proteins (eNOS and G proteins) are discussed. A better understanding of the molecular basis underlying ethnic differences in drug metabolism, transport, and response will contribute to improved individualization of drug therapy.
种族是导致个体间药物代谢和反应差异的一个重要人口统计学变量。在这个迅速发展的研究领域,已经确定了许多解释种族对药代动力学、药效学和药物安全性影响的遗传因素。本综述着重于近期的研究进展,这些进展增进了我们对造成此类种族间差异的分子机制的理解。文中讨论了可能为药物代谢酶(CYP 2C9、2C19、2D6和3A4)、药物转运体(P-糖蛋白)、药物受体(肾上腺素能受体)以及其他功能重要蛋白(内皮型一氧化氮合酶和G蛋白)的种族差异提供分子基础的基因变异。更好地理解药物代谢、转运和反应种族差异背后的分子基础,将有助于改善药物治疗的个体化。