DISPOSITION & PHARMACODYNAMICS OF COCAINE IN PREGNANCY

可卡因，一种具有积极增强作用的强大兴奋剂， 有相当数量的孕妇使用。很少有 了解该药物的处置和药效学 在怀孕期间，除了它很容易越过 胎盘和可能导致间歇性宫内缺氧， 早产，以及可能的长期发育问题。在……里面 这项建议我们计划用怀孕的母羊作为模型来研究 怀孕期间使用可卡因的某些特征，包括 可卡因在人体内处置的广泛药代动力学分析 母羊和胎儿。将对药物暴露的决定因素进行研究 一)母婴清除量；二)剂量；三)途径 给药(静脉注射与吸入挥发的游离- 碱(可卡因)；四)母体和胎儿血浆蛋白 可卡因的结合；v)与可卡因的形成和胎盘转移 可卡因代谢物。我们将比较血浆蛋白结合在 母羊和胎羔羊与孕妇和脐带静脉血 交货时取得的。我们将寻求两国之间的相互关系 可卡因与母婴的药代动力学 母体和胎儿的心血管反应和血气 血浆儿茶酚胺和胎儿行为状态。鉴于 母亲服用可卡因对其影响的观察 胎儿发育和新生儿行为，我们将确定局部 胎脑能量代谢的实验研究 (14C)-2-脱氧葡萄糖利用率。最后，我们将确定如何 心血管、神经生理和神经化学指标 胎儿和产妇的健康因同时发生的 注射可卡因和吸入热解物和 大麻的燃烧产物。这项研究的目标是 描述可卡因在母婴体内的药代动力学 并通过药效学分析，形成更清晰的 了解可卡因对老年人的急性和慢性影响 处于危险中的特殊人群的神经系统功能， 子宫内的胎儿。本研究将重点探讨其基本作用机制。 可卡因使用的作用、影响和生理危害。

Cocaine, a powerful stimulant with positive reinforcing actions, is used by a significant number of pregnant women. Very little is known about the disposition and pharmacodynamics of this drug during pregnancy, apart from the facts that it easily crosses the placenta and may cause intermittent intrauterine hypoxia, preterm labor, and possible long-term developmental problems. In this proposal we plan to use the pregnant ewe as a model to study certain features of cocaine use in pregnancy, including an extensive pharmacokinetic analysis of cocaine disposition in the ewe and fetus. Determinants of drug exposure to be studied will be i) maternal and fetal clearance, ii) dose; iii) route of administration (intravenous versus inhalation of volatilized free- base (crack) cocaine); iv) maternal and fetal plasma protein binding of cocaine; v) and formation and placental transfer of cocaine metabolites. We will compare plasma protein binding in ewe and fetal lamb with pregnant women and cord venous blood obtained at delivery. Correlations will be sought between the pharmacokinetics of cocaine and maternal and fetal cardiovascular response and blood gases, maternal and fetal plasma catecholamines, and fetal behavioral state. In view of the observations that maternally administered cocaine influences fetal development and neonatal behavior, we will determine local cerebral energy metabolism in fetal brain using the technique of (14C)-2-deoxyglucose utilization. Finally, we will determine how cardiovascular, neurophysiologic and neurochemical indexes of fetal and maternal health are altered by the simultaneous injection of cocaine and the inhalation of pyrolytic and combustion products of marijuana. The goals of this research are to describe the pharmacokinetics of cocaine in the maternal-fetal unit, and through pharmacodynamic analyses, to form a clearer understanding of the acute and chronic effects of cocaine on the function of the nervous systems of a special population at risk, fetuses in utero. This study will focus on basic mechanisms of action and effects and physiological hazards of cocaine use.