Breath Test to Rapidly Evaluate 2D6 Enzyme Activity

呼气测试快速评估 2D6 酶活性

• 批准号: 6840767
• 负责人: MITCHELL R ZAKIN
• 金额: $ 20.19万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-10 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6840767
• 关键词: biotransformation; breath tests; carbon dioxide; chemical synthesis; clinical research; cytochrome P450; dextromethorphan; diagnosis design /evaluation; drug adverse effect; drug design /synthesis /production; drug interactions; drug screening /evaluation; enzyme activity; enzyme substrate; human subject; noninvasive diagnosis; phenotype; rapid diagnosis; respiratory gas analyzer; stable isotope diagnosis

DESCRIPTION (provided by applicant): One important consequence of inter-individual variability in drug disposition and response is the risk of adverse drug reactions. In the case of pharmacogenetic variability, genotypic and phenotypic characterization of individual patients or patient populations is of interest in an attempt to predict enzyme activity and potentially optimize drug safety and efficacy. Cytochrome P450 2D6 (CYP2D6) is a clinically important pathway that has been the subject of intense investigation by virtue of its role in the biotransformation of several commonly administered drugs. The goal of the proposed research is to develop a simple, rapid, noninvasive breath test for CYP2D6 activity based on the ingestion of (O-methyl-13C)-dextromethorphan hydrobromide, a stable isotope labeled (non-radioactive) version of the well-characterized CYP2D6 phenotyping probe, dextromethorphan hydrobromide, and measurement of the 13C02/1¿C02 ratio in expired breath using commercially available instrumentation. The Phase I program has three Specific Aims: 1. Produce the labeled CYP2D6 substrate (O-methyl-13C)-dextromethorphan hydrobromide (DM) according to 2003 United States Pharmacopeia standards. 2. Demonstrate (O-methyl-13C)-DM as a phenotyping probe for CYP2D6 activity in vivo. 3. Characterize the population distribution of CYP2D6 phenotypes using the breath test. The proposed program is a collaborative effort between Physical Sciences Inc., Cambridge Isotope Laboratories, and J. Steven Leeder, Pharm.D., Ph.D in the Section of Developmental Pharmacology and Therapeutics, Children's Mercy Hospital and Clinics, Kansas City MO.

描述（由申请人提供）： 药物处置和反应中个体差异的一个重要结果是药物反应不良的风险。在药物遗传学变异性的情况下，单个患者或患者人群的基因型和表型表征是为了预测酶活性并可能优化药物安全和有效性。细胞色素P450 2D6（CYP2D6）是一种临床上重要的途径，由于其在几种常用药物的生物转化中的作用，它一直是强烈研究的主题。 The goal of the proposed research is to develop a simple, rapid, noninvasive breath test for CYP2D6 activity based on the ingestion of (O-methyl-13C)-dextromethorphan hydrobromide, a stable isotope labeled (non-radioactive) version of the well-characterized CYP2D6 phenotyping probe, dextromethorphan hydrobromide, and measurement of the 13c02/1€c02在过期的呼吸中使用市售仪器。 第一阶段计划具有三个具体目标： 1。根据2003年美国药房标准，生产标记为CYP2D6底物（O-甲基-13c） - 脱甲状腺氢脱氧液（DM）。 2。证明（O-甲基-13C）-DM作为体内CYP2D6活性的表型探针。 3。使用呼吸测试表征CYP2D6表型的种群分布。 拟议的计划是物理科学公司，剑桥同位素实验室和堪萨斯州堪萨斯城的儿童怜悯医院和诊所的物理科学公司和Pharm.D.D.D.D.D.D.D.D.D.D.D.D. D. D. D.史蒂芬·利德（J. Steven Leeder）之间的合作努力。