UW Obstetric-Fetal Pharmacology Research Unit

这项赠款建议的总体目标是在以下地点建立产科-胎儿药理学股 华盛顿大学。药理学单位的主要目标将是确定 妊娠期有治疗价值药物的药代动力学和药效学 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。这份建议书描述了 华盛顿大学建立了成功而富有成效的产科-胎儿药理学 研究小组。为了展示我们的研究兴趣和能力，以下翻译 建议进行综合我们在临床和基础科学方面的优势的研究研究，以评估 以下是研究目的。 1.我们的目标是测定细胞色素P450_2 C9和有机阳离子转运蛋白(OCT)的体内活性。 使用以下表型标记物在妊娠各阶段改变：格列本脲 用于OCT的CYP2C9和二甲双胍。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)建议进行研究，以调查怀孕对 上述药物代谢酶和转运体(中期和晚期妊娠与3个月 产后时期)。 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糖尿病的疗效和安全性。 妊娠糖尿病的治疗。建议进行第三阶段疗效和安全性试验，以评估 妊娠期糖尿病及其治疗对母儿发育的影响 来了。

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 matemal, fetal and infant / child developmental mtcomes.