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.
