Medications in Pregnancy: Defining Exposure

描述(由申请人提供)： 这是对RFA-OD-02-002的申请，目的是资助一个影响妇女健康的性别和性别因素专门研究中心，该中心由五个部门和两个学术机构共同努力。该应用程序的中心主题是“使用人类和啮齿动物范例对妊娠和哺乳期间的抗癫痫药物(AED)和精神药物进行药代动力学、药效学和药物遗传学(PK/PD/PG)建模：定义胎儿/新生儿的暴露和对产科结局的影响”该中心的主要目标包括：1)妊娠和哺乳期间抗癫痫药物(AED)和精神药物(如锂、锂)的PK/PD/PG建模。这些新数据将提供有关胎儿/新生儿接触这些药物的新陈代谢、分布和程度的信息。这个模型的数据将从患有神经疾病(癫痫、抽动症)和精神疾病(双相情感障碍、严重抑郁、强迫症、恐慌症)的妇女那里获得。这些患者群体是基于两组之间典型的慢性病程和使用类似药物的情况而选择的。来自不同疾病和种族群体的PK/PD模型增强了代谢能力和蛋白质结合的药物遗传学(PG)比较。2)这些临床数据将得到两种啮齿动物(其中一种缺乏2D6活性)的一系列实验室动物研究的补充，以提供胎儿和新生儿中枢神经系统(CNS)组织浓度、新生儿CNS清除以及出生前和出生后接触AEDs和精神药物对神经递质受体的影响。3)对这些妇女的前瞻性评估将提供所有额外接触的记录(处方药、非处方药、草药、产妇疾病事件、环境毒素)，并描述怀孕和产后的病程。这些数据的最终临床意义将是澄清影响药物代谢和分布的因素，从而提供估计的胎儿/新生儿暴露、影响这种暴露的因素，以及关于潜在的“剂量与结果”比较的新数据。该中心申请的多学科团队包括两个学术医学中心和五个部门，组成两个临床项目，一个实验室调查，由三个核心组成部分支持，以及一个具有广泛研究/临床经验的执行委员会。这些目标的实现涉及世界卫生组织《21世纪妇女健康研究议程》中提到的几个研究优先领域。

DESCRIPTION (provided by applicant): This is an application for RFA-OD-02-002 to fund a Specialized Center of Research on Sex and Gender Factors Affecting Women's Health representing the collaborative efforts of five departments and two academic institutions. The central theme of the application is "pharmacokinetic, pharmacodynamic, and pharmacogenetic (PK/PD/PG) modeling of anti-epileptic drugs (AED) and psychotropic medications during pregnancy and lactation using both human and rodent paradigms: defining fetal/neonatal exposure and influence on obstetrical outcome" ' The primary objectives of the center include: 1) PK/PD/PG modeling of anti-epileptic drugs (AED) and psychotropic medications antidepressants, lithium) during pregnancy and lactation. These novel data will provide information about the metabolism, distribution, and extent of fetal/neonatal exposure to these medications. The data for this modeling will be obtained from women with neurological disorders (Epilepsy, Tourette's Syndrome) and mental illness (Bipolar Disorder, Major Depression, Obsessive Compulsive Disorder, Panic Disorder). These patient populations were selected based on the typical chronic course of illness and utilization of similar medications between the groups. The PK/PD modeling from subjects with different illnesses and ethnic groups enhances the pharmacogenetic (PG) comparison of metabolic capacity and protein binding. 2) These clinical data will be complemented by a series of laboratory animal studies in two strains of rodent (one deficient in 2D6 activity) to provide fetal and neonatal central nervous system (CNS) tissue concentrations, neonatal CNS clearance, and neurotransmitter receptor effects of antenatal and postnatal exposure to AEDs and psychotropic medications. 3) Prospective assessment of these women will provide documentation of all additional exposures (prescription medications, over the counter preparations, herbal remedies, maternal illness events, environmental toxins) and delineation of the course of illness during pregnancy and postpartum. The ultimate clinical import of these data will be clarification of the factors influencing medication metabolism and distribution, thereby providing an estimate fetal/neonatal exposure, factors influencing such exposure, and novel data regarding the potential "dose versus outcome" comparison. The multidisciplinary team of this center application represent two academic medical centers and five departments organized into 2 clinical projects, 1 laboratory investigation, supported by 3 core components and an executive committee with extensive research/clinical experience. The achievement of the objectives address several research priority areas noted in ORWH Agenda for Research on Women's Health for the 21st century.