ORAL OXYTOCIN ANTAGONIST PHARMACODYNAMICS IN PREGNANT/NONPREGNANT RHESUS MONKEY

口服催产素拮抗剂在怀孕/非怀孕恒河猴中的药效学

• 批准号: 7561969
• 负责人: MILES J. NOVY
• 金额: $ 7.59万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7561969
• 关键词: Adverse effects; Amniotic Fluid; Animals; Blood Circulation; Blood Volume; Computer Retrieval of Information on Scientific Projects Database; Drug Kinetics; Funding; Future; Goals; Grant; Health; Human; Institution; Invasive; Macaca mulatta; Medicine; Modeling; Neonatal; Oral; Oxytocin; Oxytocin Receptor; Patient currently pregnant; Pharmaceutical Preparations; Pharmacodynamics; Plasma; Pregnancy; Premature Labor; Primates; Range; Research; Research Personnel; Resources; Source; Testing; Tocolytic Agents; United States National Institutes of Health; Uterine Contraction; Woman; drug efficacy; fetal blood; placental transfer

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. Oxytocin antagonists could help delay preterm labor, which occurs in up to 12% of all human pregnancies and contributes to a variety of neonatal health problems. Current tocolytic agents for the pharmacological inhibition of uterine contractions have side-effects and limited efficacy. The orally active AS606521 is administered in a non-invasive manner, has a slow clearance, and is specific for the oxytocin receptor. However, pregnant animals, with increased blood volume and altered circulation, may have a different clearance compared to non-pregnant animals. The direct testing of drug efficacy in reducing uterine activity in primates during pregnancy, as well as placental transfer of the drug into amniotic fluid and fetal blood, are important aspects for future use in women. The similarity of rhesus and human pregnancy allows this study to have potential direct benefits to human medicine. A pharmacokinetic and pharmacodynamic study on the orally-active oxytocin antagonist AS606521 in a nonpregnant and pregnant rhesus monkey model was initiated. The goals are to compare the pharmacokinetics of AS606521 in pregnant and non-pregnant primates, to establish the effective plasma concentration ranges for blocking oxytocin-induced uterine contractions in pregnant rhesus monkeys and to confirm the reversibility of the inhibition by higher concentrations of oxytocin (rescue therapy).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 催产素拮抗剂可以帮助延迟早产，早产发生在人类妊娠的 12% 中，并会导致各种新生儿健康问题。 目前用于药物抑制子宫收缩的保胎剂具有副作用且功效有限。口服活性 AS606521 以非侵入方式给药，清除缓慢，并且对催产素受体具有特异性。 然而，怀孕动物由于血容量增加和循环改变，与非怀孕动物相比可能具有不同的清除率。 直接测试药物在怀孕期间减少灵长类动物子宫活动的功效，以及药物通过胎盘转移到羊水和胎儿血液中，是未来在女性中使用的重要方面。 恒河猴和人类怀孕的相似性使得这项研究对人类医学具有潜在的直接益处。 在非妊娠和妊娠恒河猴模型中启动了口服活性催产素拮抗剂 AS606521 的药代动力学和药效学研究。 目标是比较 AS606521 在怀孕和非怀孕灵长类动物中的药代动力学，建立在怀孕恒河猴中阻断催产素诱导的子宫收缩的有效血浆浓度范围，并确认较高浓度催产素抑制的可逆性（救援）治疗）。