Seguí Hemanuel Arroyo, Melin Kyle, Quiñones Darlene Santiago, Duconge Jorge
School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
Department of Pharmacy Practice, School of Pharmacy, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA.
J Transl Genet Genom. 2020;4:263-277. doi: 10.20517/jtgg.2020.35. Epub 2020 Jul 30.
As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the more complex dosing required of methadone due to its long and variable half-life) and fewer prescribing limitations (may be prescribed outside the setting of federally approved clinics), the increase in buprenorphine use in the United States has been dramatic in recent years. Despite buprenorphine's demonstrated efficacy, patient-specific factors can alter the response to the medications, which may lead to treatment failure in some patients. Clinical characteristics (sex, concurrent medications, and mental health comorbidities) as well as social determinants of health (housing status, involvement with the criminal justice system, and socioeconomic status) may impact treatment outcomes. Furthermore, a growing body of data suggests that genetic variations can alter pharmacological effects and influence therapeutic response. This review will cover the available pharmacogenomic data for the use of buprenorphine in the management of opioid use disorders. Pharmacogenomic determinants that affect opioid receptors, the dopaminergic system, metabolism of buprenorphine, and adverse events are discussed. Although much of the existing data comes from observational studies, clinical research is ongoing. Nevertheless, the development of pharmacogenomic-guided strategies has the potential to reduce opioid misuse, improve clinical outcomes, and save healthcare resources.
随着阿片类药物流行在美国持续蔓延,需要接受阿片类药物使用障碍治疗的患者数量不断攀升。尽管药物辅助治疗是一种能够帮助应对这一流行趋势的高效工具,但其应用一直受到限制。尽管如此,由于丁丙诺啡的给药方案更为简便(与美沙酮相比,美沙酮因其半衰期长且变化不定,给药更为复杂),且处方限制较少(可在联邦政府批准的诊所之外开具),近年来美国丁丙诺啡的使用量急剧增加。尽管丁丙诺啡已证实具有疗效,但患者的个体因素可能会改变对药物的反应,这可能导致部分患者治疗失败。临床特征(性别、同时使用的药物以及心理健康合并症)以及健康的社会决定因素(住房状况、与刑事司法系统的关联以及社会经济地位)可能会影响治疗结果。此外,越来越多的数据表明,基因变异会改变药理作用并影响治疗反应。本综述将涵盖丁丙诺啡用于阿片类药物使用障碍管理的现有药物基因组学数据。将讨论影响阿片受体、多巴胺能系统、丁丙诺啡代谢以及不良事件的药物基因组学决定因素。尽管现有数据大多来自观察性研究,但临床研究仍在进行中。尽管如此,药物基因组学指导策略的发展有可能减少阿片类药物的滥用、改善临床结果并节省医疗资源。