PK OF LMWH AND UFH IN PREGNANCY

妊娠期间 LMWH 和 UFH 的 PK

• 批准号: 7378648
• 负责人: MARY D STEPHENSON
• 金额: $ 0.14万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-18 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378648
• 关键词: embryo /fetus; heparin; pharmacokinetics; postpartum; pregnancy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this study is to optimize prophylactic dosing of dalteparin and unfractionated heparin (UFH) in pregnancy for women with obstetrical antiphospholipid syndrome (APS) which is used to decrease maternal and fetal morbidity/mortality. The investigators' proposed dosing protocols for dalteparin and UFH need to be verified based on pharmacokinetic and pharmacodynamic parameters. AUC will be used to estimate heparin exposure prior to pregnancy, during the 1st, 2nd, and 3rd trimesters, and postpartum. Following this, a multi-centered randomized trial will be designed to compare pregnancy outcomes, as well as maternal and fetal complications, in women with APS who are desirous of a child. The following specific objectives will be addressed in this study: 1. Further define pharmacokinetic (concentration-time) and pharmacodynamic (concentration-effect) parameters for dalteparin and UFH prior to pregnancy, during the 1st, 2nd, and 3rd trimesters and postpartum. 2. Determine therapeutic responses such as live birth and lack of maternal or fetal complications, in relation to drug exposure, based on AUC. 3. Determine if the best predictor of toxicity/complications, i.e. thromboembolic events, bleeding, thrombocytopenia, osteoporosis, is cumulative heparin dosage. 4. Verify the investigators' revised dosing protocols for dalteparin and UFH prior to pregnancy, during the 1st, 2nd, 3rd trimesters and postpartum, via pharmacokinetic and pharmacodynamic parameters. 5. Document maternal and fetal complications during pregnancy for dalteparin and UFH using the revised dosing protocols.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的总体目标是优化达肝素和普通肝素（UFH）在妊娠期用于产科抗磷脂综合征（APS）女性的预防性给药，用于降低母体和胎儿的发病率/死亡率。需要根据药代动力学和药效学参数验证研究者拟定的达肝素和UFH给药方案。AUC将用于估计妊娠前、妊娠早期、妊娠中期和妊娠晚期以及产后的肝素暴露量。在此之后，将设计一项多中心随机试验，以比较妊娠结局，以及母亲和胎儿并发症，在妇女与APS谁是渴望一个孩子。 本研究的具体目标如下：1.进一步定义妊娠前、妊娠早期、妊娠中期和妊娠晚期以及产后达肝素和UFH的药代动力学（浓度-时间）和药效学（浓度-效应）参数。2.根据AUC确定与药物暴露相关的治疗反应，如活产和无母体或胎儿并发症。3.确定毒性/并发症（即血栓栓塞事件、出血、血小板减少症、骨质疏松症）的最佳预测因子是否为肝素累积剂量。4.通过药代动力学和药效学参数，验证研究者在妊娠前、妊娠早期、妊娠中期、妊娠晚期和产后修订的达肝素和UFH给药方案。5.使用修订的给药方案记录妊娠期间达肝素和UFH的母体和胎儿并发症。