Methadone population pharmacokinetics: treatment outcome in Hmong and non-Hmong

该项目的目的是促进Gavin Bart博士发展成为一名独立的多学科翻译医生-科学家，专注于影响物质使用障碍治疗结果的生物因素。特别是实验和临床药理学以及群体药代动力学方面的教学和研究培训，将为评估用于治疗成瘾性疾病的治疗方法的持续研究生涯提供必要的技能，目前成瘾性疾病占全球死亡人数的12.4%。该项目将重点放在苗族作为美沙酮维持药代动力学研究的模型人群。我们以前观察到苗族有上级治疗结果（即，1-年保留和减少尿液毒理学阳性结果）对显着较低剂量的美沙酮比我们的非苗族人口。我们假设，这种非常成功的美沙酮治疗结果，与更大的美沙酮暴露在毫克/公斤的基础上，测量为曲线下面积。具体的目的是比较美沙酮在苗族非苗族使用人口药代动力学的药代动力学和相关的治疗结果美沙酮ADC。还将获得保存的DMA库，用于未来的药物遗传学研究。苗族是一个民族独特的群体从山区的老挝。几个世纪以来，苗族种植罂粟，估计有7%-12%的鸦片种植者依赖鸦片。自20世纪70年代以来，有7万苗族移民到明尼苏达州。其中200名苗族人参加了Hennepin县医疗中心成瘾药物计划美沙酮诊所，使其成为世界上最大的美沙酮维持苗族人口。由于苗族代表了一个遗传隔离的人口很少的混合物，他们提供了一个相关的和理想的机会，药代动力学和药物遗传学研究。调查美沙酮的药代动力学在苗族相比，非苗族可能会通知新的治疗策略，可以推广到非苗族美沙酮人群。从CDA中学到的技能可以应用于其他特殊人群的治疗结果研究或用于其他成瘾性疾病的药物（或正在开发的药物）。

DESCRIPTION (provided by applicant): The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) project is to foster the development of Dr. Gavin Bart into an independent multidisciplinary translational physician-scientist focusing on the biological factors that influence substance use disorder treatment outcome. Didactic and research training in experimental and clinical pharmacology and population pharmacokinetics, in particular, will provide skills necessary for a sustained research career evaluating therapeutics used to treat the addictive diseases, which currently account for 12.4% of deaths worldwide. This project will focus on the Hmong as 'a model population for pharmacokinetic research of methadone maintenance. We previously observed that the Hmong have superior treatment outcome (i.e., 1-year retention and reduction in urine toxicology positive results) on significantly lower doses of methadone than our non-Hmong population. We hypothesize that this highly successful methadone treatment outcome, is correlated to greater methadone exposure on a milligram/kilogram basis, measured as area under the curve. The specific aims are to compare the pharmacokinetics of methadone in Hmong to non-Hmong using population pharmacokinetics and to correlate treatment outcome to methadone ADC. A bank of preserved DMA will be also obtained for future pharmacogenetic studies. The Hmong are an ethnically distinct group from the mountains of Laos. For centuries the Hmong have cultivated opium poppies and an estimated 7%-12% of opium farmers are opiate dependent. Since the 1970s, 70,000 Hmong have immigrated to Minnesota. Two hundred of these Hmong are enrolled in the Hennepin County Medical Center Addiction Medicine Program methadone clinic; making this the largest methadone maintained Hmong population in the world. Because the Hmong represent a genetically isolated population with little admixture, they provide a relevant and ideal opportunity for pharmacokinetic and pharmacogenetic research. Investigation of the pharmacokinetics of methadone in the Hmong compared to non-Hmong may inform new treatment strategies that could be generalized to non-Hmong methadone populations. The skills learned from this CDA could be applied to studies of treatment outcome in other special populations or for medications used (or in development) for other addictive diseases.