AGE AND PROPRANOLOL ENANTIOMERIC KINETICS AND DYNAMICS

年龄和普萘洛尔对映体动力学和动力学

基本信息

批准号：
3118633
负责人：
PETER J WEDLUND
金额：
$ 10.53万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-08-01 至 1991-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3118633
关键词：
aging antiarrhythmic agent antihypertensive agents beta adrenergic receptor binding proteins drug adverse effect drug metabolism drug receptors human subject propranolol racemization stereochemistry stereoisomer

项目摘要

This proposal will investigate the effect of age on propranolol steroselective disposition and response in man. Beta-receptors in the elderly appear to have a diminished in-vivo affinity for propranolol. Evidence for a change in propranolol binding to these receptors, however, has been based upon the relationship between total racemic drug levels and effect. Little is known about the influence of age on the steroselective disposition of propranolol, even though changes in its enantiomeric composition in-vivo could alter its response and influence conclusions about the diminished affinity of beta-receptors for propranolol in the aged. Recent evidence has shown the steroselective disposition of hexobarbital is altered by age in man and the possibility exists that other racemic drugs, like propranolol, may also be affected. More detailed cross-sectional studies of age related effects on propranolol steroselective disposition and in-vivo binding to beta- receptors in man are proposed which will define both the extent and rate change in these parameters with age. The specific hypothesis to be tested is: An age associated alteration in the enantiomeric disposition of propranolol occurs in man which contributes to the apparent altered sensitivity of the elderly to this drug. The testing of this hypothesis will involve a multidisciplinary team with expertise in analytical methods, protein binding and clinical procedures. This research should provide valuable basic information by delineating the influence of age on the steroselective disposition and response to propranolol.

该提议将研究年龄对普萘洛尔的影响人的静态性倾向和反应。 β受体中老年人似乎在体内的亲和力降低普萘洛尔。普萘洛尔与这些结合的变化的证据但是，受体一直基于外消毒药物水平和作用。关于年龄对普萘洛尔的静态性分配的影响，即使其体内对映体组成的变化也可以改变其反应并影响有关降低的结论 β受体对普萘洛尔的亲和力。最近的证据表明六边形的静态性处理随着人的年龄而改变，存在其他可能性像普萘洛尔这样的外消毒药物也可能受到影响。更多的年龄相关影响的详细横断面研究普萘洛尔的纯化性分配和体内结合与β- 提出了人类中的受体，这将定义并随着年龄的增长而变化这些参数。要测试的具体假设是：相关的年龄普萘洛尔的对映体处置的改变发生在人有助于明显改变的敏感性老年人对这种药物。该假设的检验将涉及具有分析方法专业知识的多学科团队，蛋白质结合和临床程序。这项研究应该通过描述的影响来提供有价值的基本信息年龄在st骨上的处置和对普萘洛尔的反应。