Indiana PREGMED

描述（由申请人提供）：在治疗学的世界里，在过去的五十年里发生了巨大的变化，使数百万人受益。产科药理学研究单位的这一应用的基本目的是带来的技能和技术，一直是治疗革命的关键，在怀孕治疗的研究。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。我们计划在我们名为PREGMED的试点中心取得成功的基础上再接再厉，该中心专注于为孕妇及其子女提供更个性化护理的研究。我们的建议涉及强大的临床产科的合成与5个关键核心：1）药物分析实验室，以测量孕妇及其子女的少量药物; 2）药物基因组学核心实验室，将使用新的高通量技术来改善治疗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来模拟药代动力学，药效学变化与药物基因组学和其他生物标志物数据一致。4)血管生成生物标志物核心旨在跟踪这些女性中药物的血管效应。5)我们认为生物伦理学核心是我们临床和基础/临床前工作不可或缺的。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类抗抑郁药对孕妇血管的影响。我们假设，SSRI代谢增加在怀孕期间导致患者暴露于SSRI和随后的抑郁症状和抑郁评分在怀孕期间恶化。为了验证这一假设，我们提出了两个目标：i）研究药物代谢酶和5-羟色胺途径的遗传多态性如何影响SSRI处置和疗效的药物代谢酶的药代动力学参数和SSRI治疗的临床疗效。

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.