Medications in Pregnancy: Defining Exposure

描述（由申请人提供）： 这是一份RFA-OD-02-002的申请，目的是资助一个影响妇女健康的性和性别因素专门研究中心，该中心代表了五个部门和两个学术机构的合作努力。该申请的中心主题是“药代动力学、药效学和药物遗传学使用人类和啮齿动物范例在妊娠和哺乳期间对抗癫痫药物（AED）和精神药物的PK/PD/PG建模：定义胎儿/新生儿暴露和对产科结局的影响”“该中心的主要目标包括：1）抗癫痫药物（AED）和精神药物（抗抑郁药，锂）在妊娠和哺乳期间的PK/PD/PG建模。这些新数据将提供有关这些药物的代谢、分布和胎儿/新生儿暴露程度的信息。该建模的数据将从患有神经系统疾病（癫痫、抽动秽语综合征）和精神疾病（双相情感障碍、重度抑郁症、强迫症、惊恐障碍）的女性中获得。这些患者人群的选择基于典型的慢性病程和组间相似药物的使用。不同疾病和种族受试者的PK/PD建模增强了代谢能力和蛋白结合的药物遗传学（PG）比较。2)这些临床数据将通过在两种啮齿动物品系（一种缺乏2D 6活性）中进行的一系列实验室动物研究进行补充，以提供胎儿和新生儿中枢神经系统（CNS）组织浓度、新生儿CNS清除率以及产前和产后暴露于AED和精神药物的神经递质受体效应。3)对这些妇女的前瞻性评估将提供所有额外暴露（处方药、非处方制剂、草药、孕产妇疾病事件、环境毒素）的文件，并描述妊娠和产后期间的病程。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、影响此类暴露的因素以及关于潜在“剂量与结局”比较的新数据。该中心申请的多学科团队代表两个学术医学中心和五个部门，分为2个临床项目，1个实验室研究，由3个核心组成部分和一个具有丰富研究/临床经验的执行委员会提供支持。这些目标的实现涉及ORWH 21世纪妇女健康研究议程中指出的几个优先研究领域。

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.