ETHNICITY AND DIFFERENTIAL RESPONSES TO BENZODIAZEPINES

该项目旨在复制和扩展以前的研究结果。 中国亚裔和高加索人正常志愿者的种族差异 苯二氮卓类药物对激发剂量的反应及其影响因素 这可能是造成这种差异的原因。两种不同的 苯二氮卓类、阿普唑仑和劳拉西潘，具有不同的药代动力学 将对属性和神经行为反应特征进行管理 非肠道的和口服的。标准的药代动力学方案将是 用于测定受试药物的血药浓度 和它们的代谢物，以及蛋白质结合的比例。 同时，眼球跳动，数字符号替代测试， 镇静程度、情绪紧张、生长激素、促肾上腺皮质激素和 皮质醇反应将用于评估 这些药物的药效学效应。无论是在外国出生的，还是在美国出生的- 出生的亚洲人将被包括在这项研究中，以评估亲属 遗传因素与环境因素对民族致病的贡献 动力学和动态反应的差异。 这项研究是我们正在进行的努力的重要组成部分 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，要理解 造成这种差异的机制。这些发现来自于 这项研究不仅在以下方面具有直接的实际意义 为临床用药提供更准确合理的指导 苯二氮卓类药物在美国和亚洲患者治疗中的应用 国际上，但将对领域做出重大贡献 药代动力学、群体药物遗传学以及现场应用 一般的精神药理学。

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.