Indiana PREGMED

印第安纳预科

基本信息

批准号：
8011457
负责人：
DAVID Alastair FLOCKHART
金额：
$ 65.81万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8011457
关键词：
Address Adverse effects Affect Alcohol consumption Antidepressive Agents Biochemical Bioethics Bioinformatics Biological Markers Blood Vessels CYP2C19 gene CYP2C9 gene CYP2D6 gene CYP3A4 gene CYP3A5 gene Caring Child Clinical Clinical Pharmacology Clinical Research Data Data Set Discipline Discipline of obstetrics Disease Dose Drug Kinetics Environment Enzymes Exposure to Fetus Fluoxetine Genes Genetic Polymorphism Goals HTR2A gene Incidence Indiana Infant Infant Development Institutional Review Boards Knowledge Laboratories Lead Link Measures Mental Depression Metabolism Modeling Mothers Neonatal Neonatology Outcome Pathway interactions Patients Pharmaceutical Preparations Pharmacodynamics Pharmacogenetics Pharmacogenomics Pharmacology Plasma Population Postpartum Depression Pregnancy Pregnancy Outcome Pregnant Women Prevalence Principal Investigator Recording of previous events Research Research Design Risk Safety Sampling Selective Serotonin Reuptake Inhibitor Serotonin Sertraline Technology Testing Therapeutic Therapeutic Studies Time Woman Work angiogenesis base child bearing clinical application clinical efficacy coping depressive symptoms drug metabolism experience high throughput technology improved innovation maternal depression neonate novel strategies pharmacokinetic model pre-clinical serotonin transporter skills success suicidal

项目摘要

DESCRIPTION (provided by applicant): Within the world of therapeutics, immense changes have occurred over the last fifty years that have benefited millions. The fundamental purpose of this application for an Obstetric Pharmacology Research Unit is to bring skills and technologies that have been key to the therapeutic revolution to the study of therapeutics in pregnancy. Within a strong academic clinical obstetric environment, we plan to exploit expertise and experience in the discipline of clinical pharmacology, which has been key to the success of the broad therapeutic revolution. We plan to build on the success of our pilot Center, entitled PREGMED, focused on research designed to deliver more individualized care to pregnant women and their children. Our proposal involves the synthesis of strong clinical obstetrics with 5 key cores: 1) a drug analytical laboratory to measure small amounts of drugs in pregnant women and their children; 2) a pharmacogenomic core laboratory that will use new high throughput technologies to improve both the targeting of therapies and our understanding of their biochemical basis 3) A computation and bioinformatics core to model pharmacokinetic, pharmacodynamic changes in concert with pharmacogenomic and other biomarker data. 4) An angiogenesis biomarker core aimed at following vascular effects of drugs in these women. 5) a bioethics core that we believe is integral to both our clinical and our basic/preclinical work. To demonstrate the collective value of these cores, we propose linked basic and clinical studies designed to test the vascular effects of the SSRI class of antidepressants in pregnant women. We hypothesize that SSRI metabolism increases during pregnancy resulting in a decrease in patient exposure to the SSRI and subsequent worsening of depressive symptoms and depression scores during pregnancy. To test this hypothesis we propose two aims: i) To investigate the pharmacokinetic parameters and clinical efficacy of SSRI therapy as pregnancy progresses and ii) to examine how genetic polymorphisms of drug metabolizing enzymes and the serotonin pathway impact SSRI disposition and efficacy.

描述（由申请人提供）：在过去的五十年里，治疗学领域发生了巨大的变化，使数百万人受益。产科药理学研究单位的这一应用程序的根本目的是将治疗革命的关键技能和技术引入妊娠治疗研究。在强大的学术临床产科环境中，我们计划利用临床药理学学科的专业知识和经验，这是广泛的治疗革命成功的关键。我们计划以我们名为 PREGMED 的试点中心的成功为基础，重点开展旨在为孕妇及其子女提供更加个性化护理的研究。我们的建议涉及综合具有 5 个关键核心的强大临床产科：1）药物分析实验室，用于测量孕妇及其孩子的少量药物； 2) 药物基因组核心实验室，将使用新的高通量技术来改善治疗的靶向性和我们对其生化基础的理解 3) 计算和生物信息学核心，用于与药物基因组和其他生物标志物数据相一致地模拟药代动力学、药效变化。 4) 血管生成生物标志物核心，旨在跟踪药物对这些女性的血管作用。 5）我们认为生物伦理学核心是我们的临床和基础/临床前工作不可或缺的一部分。为了证明这些核心的集体价值，我们建议进行相关的基础研究和临床研究，旨在测试 SSRI 类抗抑郁药对孕妇的血管作用。我们假设妊娠期间 SSRI 代谢增加，导致患者接触 SSRI 的减少，并随后导致妊娠期间抑郁症状和抑郁评分恶化。为了检验这一假设，我们提出了两个目标：i) 研究妊娠过程中 SSRI 治疗的药代动力学参数和临床疗效，ii) 检查药物代谢酶和血清素途径的遗传多态性如何影响 SSRI 的处置和疗效。