UW Obstetric-Fetal Pharmacology Research Unit

描述（由申请人提供）：本基金提案的总体目标是在华盛顿大学建立一个产科-胎儿药理学单位。药理学单元的主要目标将是表征药物的药代动力学和药效学，这些药物在妊娠期间具有治疗价值，并且其临床药理学会因妊娠状态而改变。总体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可用环境和资源。为了证明我们的研究兴趣和能力，我们提出了以下整合我们在临床和基础科学方面优势的转化研究，以评估以下研究目标。 1.我们的目的是使用以下表型标志物确定CYP 2C 9和有机阳离子转运蛋白（OCT）的体内活性是否在妊娠阶段发生变化：格列本脲用于CYP 2C 9，二甲双胍用于OCT。I期（群体药代动力学分析）和II期（药代动力学/药效学分析）研究拟调查妊娠对上述药物代谢酶和转运蛋白的影响（第二和第三孕期与产后3个月）。 2.我们的目的是确定胰岛素、格列本脲、格列本脲加二甲双胍治疗妊娠期糖尿病的疗效和安全性。一项III期疗效和安全性试验拟评估妊娠期糖尿病以及治疗对母体、胎儿和婴儿/儿童发育结局的影响。

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.