UW Obstetric-Fetal Pharmacology Research Unit

华盛顿大学产胎儿药理学研究单位

基本信息

批准号：
7354428
负责人：
MARY F HEBERT
金额：
$ 1.6万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2007-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7354428
关键词：
Adult Andro-Diane Animal Model Animals Applications Grants Area Basic Science Biochemical CYP2C9 gene Child Chronic Disease Clinical Clinical Data Clinical Pharmacology Clinical Trials Condition Cytochrome P450 Data Development Discipline of obstetrics Disease Dose Drug Kinetics Drug usage Elderly Environment Enzymes Exposure to Fetus Funding Gestational Diabetes Glyburide Goals Health Professional In Vitro Infant Insulin Label Membrane Transport Proteins Metformin Natural History Numbers Organ Organic Cation Transporter Orphan Patient currently pregnant Performance Pharmaceutical Preparations Pharmacodynamics Pharmacogenetics Pharmacology Pharmacotherapy Phase Phenotype Physicians Physiological Population Postpartum Period Pre-Clinical Model Pregnancy Pregnant Women Research Research Infrastructure Resources Safety Scientist Site Specialist Staging System Technology Testing Therapeutic Third Pregnancy Trimester Time Today Toxic effect Training Translational Research United States Food and Drug Administration Universities Washington Woman Work base drug efficacy experience fetal in vivo interest men models and simulation named group news nonhuman primate pharmacokinetic model placental transfer research study

项目摘要

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.

该拨款提案的总体目标是在该机构建立产科-胎儿药理学单位华盛顿大学。药理学单元的主要目标是表征妊娠期间具有治疗价值的药物的药代动力学和药效学临床药理学会因怀孕状态而改变。一般研究重点是细胞色素 P450 酶和膜转运蛋白。该提案描述了可用的环境和资源华盛顿大学建立了成功且富有成效的产科胎儿药理学研究单位。为了展示我们的研究兴趣和能力，以下翻译建议整合我们在临床和基础科学方面的优势进行研究，以评估以下研究目标。 1. 我们的目的是确定CYP2C9和有机阳离子转运蛋白（OCT）的体内活性是否使用以下表型标记在妊娠阶段发生改变：格列本脲用于 OCT 的 CYP2C9 和二甲双胍。 I 期（群体药代动力学分析）和 II 期（药代动力学/药效分析）研究旨在调查妊娠对上述药物代谢酶和转运蛋白（妊娠中期和晚期 vs. 3 个月）产后期）。 2. 我们的目标是确定胰岛素与格列本脲与格列本脲加二甲双胍的疗效和安全性妊娠期糖尿病的治疗。建议进行 III 期疗效和安全性试验来评估妊娠糖尿病的影响以及对母亲、胎儿和婴儿/儿童发育的治疗 mtcomes。