PHARMACOGENETICS AND DRUG INTERACTIONS

药物遗传学和药物相互作用

• 批准号: 7606014
• 负责人: TIMOTHY S. TRACY
• 金额: $ 7.93万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606014
• 关键词: Anti-Inflammatory Agents; Anti-inflammatory; Antifungal Agents; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Data; Drug Interactions; Enzymes; Fluconazole; Flurbiprofen; Funding; Genetic; Genotype; Grant; Ibuprofen; Individual; Institution; Laboratories; Mediating; Metabolism; Pharmaceutical Preparations; Pharmacogenetics; Population; Research; Research Personnel; Resources; Source; Subgroup; United States National Institutes of Health; human CYP2C9 protein; inhibitor/antagonist

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project will examine the pharmacogenetics of flurbiprofen in the absence and presence of fluconazole. Flurbiprofen is a non-steriodal anti-inflammatory drug, similar to ibuprofen. Flubiprofen metabolism is a marker for the body's ability to metabolize drugs via the cytochrome P450 2C9 enzyme. Fluconazole, an anti-fungal drug, is an established inhibitor of metabolism by this same enzyme. It has also been established that individuals possessing the *3 genotype (genetic subtype) of cytochrome P450 2C9 have lower capacity to metabolize drugs like flurbiprofen than do individuals having the most common genotype (*1). Data from our laboratory suggest that individuals with the *3 genotype should also be less susceptible to inhibition of cytochrome P450 2C9 mediated metabolism of flurbiprofen than individuals with the *1 genotype. Thus, subjects will be screened for their individual cyrochrome P450 2C9 genotype and two subgroups identified (individuals possessing only the *1 subtype and individuals possessing a mixture of the *1/3* subtypes). We will study individuals with the *1/*3 genotypes (since the *3/*3 genotype is so rare in the population) and compare them to individuals with the most common genotype (*1/*1).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目将研究氟比洛芬在不存在和存在氟康唑的情况下的药物遗传学。 氟比洛芬是一种非甾体类抗炎药，与布洛芬类似。氟比洛芬代谢是身体通过细胞色素 P450 2C9 酶代谢药物能力的标志。 氟康唑是一种抗真菌药物，是这种酶代谢的既定抑制剂。 还已确定，具有细胞色素 P450 2C9 *3 基因型（遗传亚型）的个体代谢氟比洛芬等药物的能力低于具有最常见基因型的个体 (*1)。 我们实验室的数据表明，与*1 基因型个体相比，*3 基因型个体也更不易受到细胞色素 P450 2C9 介导的氟比洛芬代谢抑制的影响。 因此，将筛选受试者的个体cyrochrome P450 2C9基因型和鉴定的两个亚组（仅具有*1亚型的个体和具有*1/3*亚型混合的个体）。我们将研究具有 *1/*3 基因型的个体（因为 *3/*3 基因型在人群中非常罕见），并将其与具有最常见基因型 (*1/*1) 的个体进行比较。