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

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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.