Alprazolam and Simulated Driving Performance: Next Day Effects

阿普唑仑和模拟驾驶表现：次日效应

• 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
• 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

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.

摘要 吸毒后驾车以及相关的交通事故和死亡人数显著上升， 美国在过去的十年里。虽然非法物质占毒品驾驶的大部分 在某些情况下，有一些处方药也会损害驾驶能力。最令人担忧的是 在假定的治疗作用持续时间后可能损害驾驶能力的处方药。这 当FDA强制要求所有含有唑吡坦的催眠药重新贴标签时， 由于即使在8小时后也存在潜在的损害药物血液浓度的作用， 严重程度有性别差异与男性相比，女性的这种影响加剧。阿普唑仑股份 唑吡坦的许多药理学特性和汇集的证据表明，它也可能导致 超过拟定治疗作用持续时间的长期精神损害。本计画提出 这项研究招募了相同数量的男性和女性健康志愿者，他们将参加六个通宵的研究。 评估阿普唑仑是否对认知或心理表现有负面影响的会议， 与阳性和阴性对照相比。性能在一个高度 在服药前和服药后的早晨，将对具有高外部效度的复杂驾驶模拟器进行测试 局这项随机双盲研究将测试三种治疗剂量的阿普唑仑， 潜在损害剂量唑吡坦和安慰剂的混合因子设计-每例受试者接受所有 药物条件。为了评价性别是否会影响第二天阿普唑仑的作用，将性别作为一个中间变量进行分析- 主体因素。拟议的实验将使用敏感的行为和分析评估， 关于阿普唑仑以前未探索的性质的定量和定性数据。鉴于 在美国的药物驾驶，从这项研究中获得的模拟驾驶数据将有显着 公共健康和安全影响。