Pharmacogenetics of Opioid Agonist Therapy

阿片类激动剂治疗的药物遗传学

• 批准号: 8628541
• 负责人: Wade H Berrettini
• 金额: $ 25.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628541
• 关键词: Address; Admission activity; African American; Age; Agonist; Alleles; American; Biological Markers; Blood; Brain; Buprenorphine; Chronic; Clinical; Clinical Trials Network; DNA; Data; Disease; Eligibility Determination; Epidemic; Equation; Ethnic Origin; European; Evaluable Disease; FDA approved; Gender; Gene Frequency; Genes; Genotype; Hepatotoxicity; Heroin; Heroin Dependence; Individual; Interview; Introns; Lead; Linkage Disequilibrium; Measures; Medical Records; Medical center; Medicine; Methadone; Methods; Naloxone; National Institute of Drug Abuse; Opiate Addiction; Opioid; Opioid Receptor; Outcome Measure; Patients; Persons; Pharmaceutical Preparations; Pharmacogenetics; Phenotype; Philadelphia; Physicians; Population; Preclinical Drug Evaluation; Preparation; Probability; Property; Receptor Gene; Relative Risks; Research; Sampling; Screening Result; Serum; Single Nucleotide Polymorphism; Structure; System; Testing; Therapeutic; Transaminases; Treatment outcome; United States Department of Veterans Affairs; United States Substance Abuse and Mental Health Services Administration; Urine; Variant; Venous blood sampling; Woman; arm; design; improved; kappa opioid receptors; liver function; mu opioid receptors; open label; prescription opioid; prescription opioid abuse; public health relevance; research study; response; substance abuse treatment; treatment center

Abstract Methadone (MET) and buprenorphine/naloxone (BUP) are two distinct FDA-approved agonist medications for treatment of opioid addiction. There are prominent pharmacologic differences between BUP and MET. MET is a full mu agonist, while BUP is a partial mu agonist~ BUP has kappa antagonist properties, while MET is devoid of kappa antagonism. At present it is not possible to use clinical or biomarker predictors to determine who will most likely benefit from one medication versus the other. Recent research has suggested that a common variation in the delta opioid receptor gene (OPRD1), single nucleotide polymorphism (SNP) rs678849, may predict response (urine drug screen for illicit opioids) among African-Americans (AAs) to these medications. AA opioid addicts with a CC genotype at rs678849 have a greater probability of gaining substantial therapeutic benefit from MET, while those with alternative genotypes (C/T + TT) have a greater probability to responding well to BUP (relative risk = 2.8~ p = 2.2 x 10-5). The current project represents an attempt to confirm the original finding in an independent population. Individuals of AA ethnicity, age at least 18, being treated with methadone (n = 150) or buprenorphine/naloxone (n = 150) for opioid addiction at treatment centers in New Haven and the Philadelphia Veterans Administration Medical Center, will be invited to participate. Participation involves review of medical records (to determine eligibility and response to treatment), a brief semi-structured interview and a single small (5 ml) venous blood sample. Blood will be used for DNA extraction and the rs678849 SNP will be genotyped. Genotype x treatment interaction analysis is planned, including as co-variates age, gender, age-at-onset of opioid addiction, co-morbid disorders~ urine drug screen results for opioids during the most recent 20 weeks is the sole endpoint. This phenotype will be analyzed also using generalized estimating equation methods, with the urine drug screen results treated as repeated measures. If the original observation is confirmed, this research may lead to a simple and inexpensive test for optimal agonist treatment of opioid addiction among African- Americans.

抽象的 美沙酮（MET）和丁丙诺啡/纳洛酮（BUP）是两个不同的FDA批准的激动剂 治疗阿片类药物成瘾的药物。 BUP之间存在明显的药理差异 并见面。 MET是一个完整的MU激动剂，而BUP是部分MU激动剂〜BUP具有Kappa拮抗剂的特性， 而MET缺乏Kappa的拮抗作用。 目前不可能使用临床或生物标志物预测因子 确定谁最有可能从一种药物中受益，而另一种药物则受益。 最近的研究已有 提出三角洲阿片受体基因（OPRD1），单核苷酸多态性的常见变化 （SNP）rs678849，可以预测非洲裔美国人（AAS）的反应（非法阿片类药物的尿液筛查） 这些药物。 rs678849的CC基因型的AA阿片类药物瘾君子具有更大的可能性 MET的实质性治疗益处，而具有替代基因型（C/T + TT）的治疗益处更大 对BUP响应良好的概率（相对风险= 2.8〜P = 2.2 x 10-5）。 当前的项目代表了在独立人群中确认原始发现的尝试。 AA种族的个体，至少18岁，用美沙酮（n = 150）或丁丙诺啡/纳洛酮治疗 （n = 150）纽黑文和费城退伍军人管理中心的阿片类药物成瘾 医疗中心将被邀请参加。 参与涉及对病历的审查（确定 资格和对治疗的反应），短暂的半结构访谈和一次小（5 ml）静脉血 样本。 血液将用于DNA提取，RS678849 SNP将进行基因分型。基因型X 计划进行治疗相互作用分析，包括随着年龄的年龄，性别，阿片类药物年龄的变化 成瘾，合并症〜最近20周内阿片类药物的尿液药物筛查结果是 唯一的端点。 该表型也将使用通用估计方程方法进行分析， 尿液药物筛查结果被视为重复测量。如果确认了最初的观察，这项研究 可能会导致简单且廉价的测试，用于在非洲 - 美国人。