Tzvetkov Mladen V
Department of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany.
Pharmacogenomics. 2017 Nov;18(16):1515-1523. doi: 10.2217/pgs-2017-0095. Epub 2017 Oct 24.
Beside drug metabolizing enzymes alsogenetically variable membrane transporters may substantially contribute to the interindividual variability in pharmacokinetics and efficacy of opioids and other analgesics. The organic cation transporter OCT1 is strongly expressed in the sinusoidal membrane of the human liver. It may affect hepatic uptake and thus limit metabolic rates. OCT1 is highly genetically variable. Genetic polymorphisms lead to substantially reduced OCT1 activity in up to 9% of the Europeans and the white Americans. This review summarize the data on the effect of OCT1 polymorphisms on pharmacokinetics and efficacy of opioids like morphine, codeine, and tramadol and of anti-migraine drugs. It discuss currently possible applications and perspectives for establishing OCT1 pharmacogenetics as a useful tool in personalized pain management.
除了药物代谢酶外，遗传可变的膜转运蛋白也可能在很大程度上导致阿片类药物和其他镇痛药在药代动力学和疗效方面的个体间差异。有机阳离子转运体OCT1在人肝脏的窦状膜中强烈表达。它可能影响肝脏摄取，从而限制代谢率。OCT1具有高度的遗传变异性。基因多态性导致高达9%的欧洲人和美国白人中OCT1活性大幅降低。本综述总结了OCT1基因多态性对吗啡、可待因和曲马多等阿片类药物以及抗偏头痛药物的药代动力学和疗效影响的数据。它讨论了目前将OCT1药物遗传学作为个性化疼痛管理有用工具的可能应用和前景。
