Indiana PREGMED

描述(申请人提供)：在治疗学的世界里，在过去的50年里发生了巨大的变化，使数百万人受益。申请产科药理学研究单位的基本目的是将对治疗革命至关重要的技能和技术带到怀孕治疗学研究中。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。我们计划在我们名为PREGMED的试点中心的成功基础上再接再厉，该中心专注于旨在为孕妇及其子女提供更个性化护理的研究。我们的建议涉及合成具有5个关键核心的强大的临床产科：1)一个药物分析实验室，以测量孕妇及其子女中的少量药物；2)一个药物基因组核心实验室，它将使用新的高通量技术来改进治疗的靶向性和我们对其生物化学基础的了解；3)一个计算和生物信息学核心，用于模拟药代动力学、药效变化以及与药物基因组和其他生物标记物数据相一致的变化。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影响。5)我们认为对我们的临床和基础/临床前工作都不可或缺的生物伦理学核心。为了证明这些核心的集体价值，我们提出了相关的基础和临床研究，旨在测试SSRI类抗抑郁药在孕妇中的血管效应。我们假设怀孕期间SSRI代谢增加，导致患者暴露于SSRI的减少，并随后在怀孕期间抑郁症状和抑郁评分恶化。为了验证这一假说，我们提出了两个目标：i)研究SSRI治疗随着妊娠进展的药代动力学参数和临床疗效；ii)研究药物代谢酶基因多态和5-羟色胺途径如何影响SSRI的处置和疗效。

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.