Indiana PREGMED

印第安纳预科

基本信息

批准号：
8600300
负责人：
DAVID M. HAAS
金额：
$ 88.93万
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 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8600300
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）：在治疗学领域，在过去的五十年中，发生了巨大变化。本申请的产科药理学研究部门的基本目的是为治疗革命至关重要的技能和技术带来妊娠治疗学研究。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，这是广泛治疗革命成功的关键。我们计划以题为“预先策划”的飞行员中心的成功为基础，专注于旨在为孕妇及其子女提供更多个性化的护理的研究。我们的建议涉及与5个关键核心强大的临床产科合成：1）一种药物分析实验室，用于测量孕妇及其子女的少量药物； 2）一种药物基因组核心实验室，该实验室将使用新的高通量技术来改善疗法的靶向和我们对其生化基础的理解3）计算和生物信息学核心，以模拟与药代动力学，药态动力学变化，以便与药物基因组和其他生物标志物数据结合使用。 4）血管生成生物标志物核心旨在遵循这些女性药物的血管作用。 5）我们认为这是我们的临床和基本/临床前工作不可或缺的生物伦敦核心。为了证明这些核心的集体价值，我们提出了相关的基本和临床研究，旨在测试孕妇SSRI类抗抑郁药的血管作用。我们假设在怀孕期间，SSRI代谢增加，导致患者暴露于SSRI，随后怀孕期间的抑郁症状和抑郁评分恶化。为了检验该假设，我们提出了两个目的：i）研究随着妊娠的进展，SSRI治疗的药代动力学参数和临床疗效，ii）ii）检查药物代谢酶的遗传多态性如何影响SSRI的分配和效率。