Alprazolam and Simulated Driving Performance: Next Day Effects

阿普唑仑和模拟驾驶表现：次日效应

基本信息

批准号：
9455117
负责人：
Marion Amanda Coe
金额：
$ 5.25万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9455117
关键词：
Accidents Acute Adult Alcohols Alprazolam Anxiety Anxiety Disorders Area Automobile Driving Autopsy Behavioral Benzodiazepines Binding Sites Biological Assay Blood CYP3A4 gene Clinical Research Clinical Trials Commuting Control Groups Dangerousness Data Data Analyses Data Collection Diazepam Dose Double-Blind Method Drug Controls Drug Evaluation Drug Prescriptions Enrollment Evaluation Female Funding Guidelines Hour Impairment International Intoxication Investigation Label Light Marketing Measurement Measures Molecular Monitor Motor Vehicles National Institute of Drug Abuse Outcome Measure Panic Disorder Performance Pharmaceutical Preparations Pharmacodynamics Pharmacology Phase I Clinical Trials Physiological Placebo Control Placebos Plasma Policies Positioning Attribute Prevalence Property Psychomotor Impairments Psychomotor Performance Public Health Randomized Recommendation Research Research Design Research Priority Safety Severities Sex Characteristics Sleep disturbances Sleeplessness Statutes and Laws Testing Therapeutic Time Traffic accidents United States United States Food and Drug Administration United States National Institutes of Health Woman base behavioral outcome cognitive performance design drug clearance drugged driving experimental study gender difference hangover healthy volunteer hypnotic impaired driving performance killings male men primary outcome receptor research clinical testing response secondary outcome sedative sex standard measure volunteer zolpidem

项目摘要

ABSTRACT There has been a significant rise in drugged driving, and associated traffic accidents and fatalities, in the United States over the last decade. While illegal substances account for the majority of drugged–driving cases, there are a number of prescription medications that can also impair driving ability. Most concerning are the prescription drugs which may impair driving ability after the presumed duration of therapeutic action. This phenomenon was highlighted when the FDA mandated relabeling of all hypnotic drugs containing zolpidem due to the presence of potentially impairing blood concentrations of the drug even after 8 hours; an effect that had sex-specific in its severity. This effect was exacerbated in females compared to males. Alprazolam shares many pharmacological properties with zolpidem and converging evidence suggests it may also cause prolonged psychomotor impairment beyond the proposed therapeutic duration of action. This project proposes a study enrolling an equal number of male and female healthy volunteers who will participate in six overnight sessions to evaluate if alprazolam has a negative impact on cognitive or psychomotor performance the morning after administration compared to positive and negative controls. Performance on a highly sophisticated driving simulator with high external validity will be tested before and the morning after drug administration. This randomized, double-blind study will test three therapeutic doses of alprazolam, a potentially impairing dose of zolpidem, and placebo in a mixed-factorial design—with each subject receiving all drug conditions. To evaluate if sex influences next-day alprazolam effects, sex will be analyzed as a between- subjects factor. The proposed experiment will use sensitive behavioral and analytic assessments to yield quantitative and qualitative data on previously unexplored properties of alprazolam. In light of the prevalence of drugged driving in the United States, the simulated driving data obtained from this study will have significant public health and safety implications.

抽象的药后驾驶以及相关的交通事故和死亡人数显着增加过去十年来，美国的毒驾事件中，非法药物占了大多数。在某些情况下，有许多处方药也会损害驾驶能力。在预计的治疗作用持续时间后可能损害驾驶能力的处方药。当 FDA 要求对所有含有唑吡坦的安眠药重新贴上标签时，这一现象就凸显出来了由于即使在 8 小时后也可能会损害药物的血液浓度；与阿普唑仑相比，其严重程度具有性别特异性。唑吡坦的许多药理学特性和综合证据表明，它也可能导致该项目提出了超出建议的治疗作用持续时间的精神性长期运动障碍。一项招募同等数量男性和女性健康志愿者的研究，他们将参加六次过夜评估阿普唑仑是否对认知或精神运动表现产生负面影响的课程与阳性和阴性对照相比，早晨给药后的表现较高。具有高外部效度的复杂驾驶模拟器将在用药前和用药后早晨进行测试这项随机、双盲研究将测试阿普唑仑的三种治疗剂量。在混合因素设计中，唑吡坦和安慰剂的剂量可能会受到损害——每个受试者都接受所有治疗为了评估性别是否影响第二天的阿普唑仑效果，将性别作为中间变量进行分析。拟议的实验将使用敏感的行为和分析评估来产生结果。鉴于阿普唑仑的流行程度，提供了有关阿普唑仑先前未探索的特性的定量和定性数据。对于美国毒驾的调查，本研究获得的模拟驾驶数据将具有重要意义。公共健康和安全影响。