ETHNICITY AND DIFFERENTIAL RESPONSES TO BENZODIAZEPINES

该项目旨在复制和扩展以前的研究结果， 亚洲和高加索正常志愿者之间的种族差异 对苯二氮卓类药物激发剂量的反应，并探索影响因素 这可能是造成这种差异的原因。 两个不同 苯二氮卓类、阿普唑仑和劳拉西泮，具有不同的药代动力学 将管理属性和神经行为反应概况 肠胃外和口服。 标准药代动力学方案将 用于测定试验药物的血浆浓度 及其代谢产物和蛋白质结合比例。 同时，扫视眼动，数字符号替代测试， 镇静水平、情绪状态、生长激素、ACTH和 皮质醇反应将用于评估 这些药物的药效。 外国出生的和美国出生的- 出生的亚洲人将被纳入本研究，以评估相对 遗传与环境因素在种族差异中的作用 动力学和动力学响应的差异。 这项研究是我们正在进行的努力的一个重要组成部分， 不仅澄清了种族差异的存在和程度， 精神反应，但更重要的是，了解 造成这种差异的机制。 研究结果来自 这项研究不仅在以下方面具有直接的实际意义： 为临床使用提供更准确、合理的指导 苯二氮卓类药物治疗亚洲患者在美国和 国际上，但将大大有助于该领域的 药代动力学，群体药物遗传学，以及该领域 精神药理学的一部分

This project aims to replicate and expand previous findings reagrding ethnic differences between Asian and Caucasian normal volunteers in response to challenge doses of benzodiazepines and to explore factors that might be responsible for such differences. Two different benzodiazepines, alprazolam and lorazepam, with distinct pharmacokinetic properties and neurobehavioral response profiles will be administered parenterally and orally. Standard pharmacokinetic protocols will be utilized for the measurement of plasma concentrations of the test drugs and their metabolites, and proportions of protein-binding. Concurrently, saccadic eye movement, digital symbol substitution test, Level of sedation, changes in mood ststes, growth hormone, ACTH, and cortisol responses will be used for the assessment of the pharmacodynamic effects of these drugs. Both foreign-born and American- born Asians will be included in this study to assess the relative contribution of genetic vs environment factors in contributing to ethnic differences in the kinetic and dynamic responses. This study represents an important part of our on0going efforts in clarifying not only the existence and extent of ethnic differences in psychotropic responses, but even more importantly, to understand the mechanisms responsible for such differences. The findings derived from this study will not only have immediate practical relevance in terms of providing more precise and rational guidelines for the clinical use of benzodiazepines in treating Asian patients both in the Unites States and internationally, but will contribute significantly to the field of pharmacokinetics, population pharmacogenetics, as well as to the field of psychopharmacology in general.