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：
7895314
负责人：
MARY F HEBERT
金额：
$ 86.82万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7895314
关键词：
Adult Animal Model Animals Applications Grants Area Basic Science Biochemical CYP2C9 gene Child Chronic Disease Clinical Clinical Data Clinical Pharmacology Clinical Trials 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 Organ Organic Cation Transporter Orphan Outcome 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 Toxic effect Training Translational Research Universities Washington Woman Work base clinical material drug efficacy experience fetal in vivo interest men models and simulation named group news nonhuman primate pharmacokinetic model placental transfer pregnant research study safety study

项目摘要

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.

描述（由申请人提供）：该赠款提案的总体目标是在华盛顿大学建立一个产科药理学部门。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，并且其临床药理学因孕妇状态而改变。一般研究重点是细胞色素P450酶和膜转运蛋白。该建议描述了华盛顿大学的可用环境和资源，以建立成功且富有生产力的产科药理学研究部门。为了证明我们的研究兴趣和能力，提出了以下转化研究，这些研究将我们在临床和基本科学中的优势整合到评估以下研究的目的。 1。我们旨在确定使用以下表型标记物通过妊娠阶段改变了CYP2C9和有机阳离子转运蛋白（OCT）的体内活性：CYP2C9的Glyburide和OCT的二甲双胍。提出了I期（人群药代动力学分析）和II期（药代动力学 /药效分析）研究，以研究妊娠对上述药物 - 代谢酶和转运蛋白的影响（第二和第三个三个月和产后三个月）。 2。我们的目标是确定胰岛素与格列本卷与格列本伯里德的疗效和安全性以及二甲双胍治疗妊娠糖尿病。提出了一项III期疗效和安全试验，以评估妊娠糖尿病的影响以及对孕产妇，胎儿和婴儿 /儿童发育效果的治疗。