UW Obstetric-Fetal Pharmacology Research Unit

描述(由申请者提供)：这项拨款提案的总体目标是在华盛顿大学建立一个产科-胎儿药理学部门。药理学股的主要目标将是确定怀孕期间具有治疗价值的药物的药代动力学和药效学特征，这些药物的临床药理会因怀孕状态而改变。一般的研究重点将是细胞色素P450酶和膜转运蛋白。该提案描述了华盛顿大学建立一个成功和富有成效的产科-胎儿药理学研究单位的现有环境和资源。为了展示我们的研究兴趣和能力，我们建议对以下研究目标进行评估，这些研究整合了我们在临床和基础科学方面的优势。 1.我们的目标是利用以下表型标记物：格列本脲用于CYP2C9和二甲双胍用于有机阳离子转运蛋白(OCT)，以确定在不同的妊娠阶段中，细胞色素P450_2C9和有机阳离子转运体(OCT)的活性是否发生改变。建议进行第一阶段(群体药代动力学分析)和第二阶段(药代动力学/药效学分析)研究，以调查怀孕对上述药物代谢酶和转运体(怀孕中期和晚期与产后3个月)的影响。 2.我们的目标是比较胰岛素、格列本脲和格列本脲加二甲双胍治疗妊娠期糖尿病的疗效和安全性。第三阶段的有效性和安全性试验被提议用来评估妊娠期糖尿病的影响以及治疗对母体、胎儿和婴幼儿发育结果的影响。

DESCRIPTION (provided by applicant): The overall objective of this grant proposal is to establish an Obstetric-Fetal Pharmacology Unit at the University of Washington. The major goal of the pharmacology unit will be to characterize the pharmacokinetics and pharmacodynamics of drugs that are of therapeutic value during pregnancy and whose clinical pharmacology is altered by the pregnant state. The general research focus will be cytochrome P450 enzymes and membrane transporters. This proposal describes the available environment and resources at the University of Washington for establishing a successful and productive Obstetric-Fetal Pharmacology Research Unit. As a demonstration of our research interests and capabilities the following translational research studies that integrate our strengths in clinical and basic sciences are proposed to evaluate the following study aims. 1. We aim to determine whether the in vivo activities of CYP2C9 and organic cation transporter (OCT) are altered through stages of pregnancy using the following phenotype markers: glyburide for CYP2C9 and metformin for OCT. Phase I (population pharmacokinetic analysis) and Phase II (pharmacokinetic / pharmacodynamic analysis) studies are proposed to investigate the effects of pregnancy on the aforementioned drug-metabolizing enzymes and transporters (second and third trimesters vs. 3 months postpartum period). 2. We aim to determine the efficacy and safety of insulin vs. glyburide vs. glyburide plus metformin for treatment of gestational diabetes mellitus. A Phase III efficacy and safety trial is proposed to evaluate the effects of gestational diabetes as well as the treatments on maternal, fetal and infant / child developmental outcomes.