Clinical Pharmacology of Electronic Cigarettes

电子烟的临床药理学

• 批准号: 9063499
• 负责人: NEAL L BENOWITZ
• 金额: $ 70.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9063499
• 关键词: Acetylcysteine; Acrolein; Address; Aerosols; Affect; Area; Biological; Biological Assay; Biological Markers; Blood; Blood Pressure; Breathing; Cardiovascular system; Catecholamines; Characteristics; Cigarette; Cigarette Smoker; Circadian Rhythms; Clinical; Clinical Data; Clinical Pharmacology; Clinical Research; Collection; Cotinine; Deglutition; Devices; Dose; Drug Kinetics; Electronic cigarette; Ensure; Excretory function; Exhalation; Exposure to; Gastrointestinal tract structure; Glycerol; Growth; Health; Heart Rate; Hormonal; Hour; Human; Industry; Intake; Intention; Knowledge; Learning; Liquid substance; Lung; Marketing; Measurement; Measures; Methods; Minor; Modality; Monitor; Nicotine; Nicotine Dependence; Odors; Oropharyngeal; Outpatients; Pattern; Process; Propylene Glycols; Regulation; Rewards; Risk; Safety; Self Administration; Sensitivity and Specificity; Smoking; Smoking Behavior; Source; Study Subject; Time; Titrations; Tobacco; Tobacco smoke; Tobacco use; United States Food and Drug Administration; Urine; Validation; Withdrawal; Withdrawal Symptom; addiction; base; cost; craving; design; experience; propylene oxide; sample collection; satisfaction; smoking cessation; toxicant; urinary; volatile organic compound; voltage; ward

 DESCRIPTION (provided by applicant): Electronic cigarettes (EC) are nicotine delivery devices that generate a nicotine-containing aerosol which is inhaled by the user. EC are perceived by users to be useful in helping quitting smoking of conventional tobacco cigarettes (TC) as well as having a presumed lower risk of adverse health effects compared to TC, the potential for use in public places, reduced cost, and lack of the noxious clinging odors associated with TC use. The use of EC has dramatically grown in recent years and is currently estimated to be a billion dollar industry, with over 400 existing brands of EC and the three major U.S. tobacco companies now marketing their own brands. The FDA has announced the intention to regulate EC. Key questions relevant to FDA regulation include the addictiveness and safety of EC. Many believe that EC function as nicotine delivery devices in the same way as TC, and that EC will prove to be just as addictive as TC, but this may not be the case because of fundamental differences in the design and method of use of these products. For example, we hypothesize that systemic nicotine exposure will be lower with EC compared to TC; that despite lower nicotine intake EC users will experience similar reward and no greater withdrawal symptoms or craving compared to TC; and that dual EC/ TC users will not titrate their daily intake of nicotine in the same way that TC smokers of high- vs low-yield nicotine TC do. Our proposal specifically focuses on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving. We will also examine aspects of safety of EC use (by assessment of cardiovascular and hormonal effects of use and of biomarkers of exposure to potentially toxic constituents) and explore the identification and validation of biomarkers that may be useful in distinguishing EC from TC use. Study subjects will be dual users of TC and EC so that we may compare both modalities of use in experienced users in a within-subject design. The study will consist of two 1-week blocks (EC-only or TC-only conditions) with 4 days of outpatient ad libitum product use followed by 3 days in a clinical research ward to include a single-use pharmacokinetic study, monitoring of product use, subjective assessments, blood and urine collections to assess biomarkers, and a 24-hour period of cardiovascular monitoring. Two additional days at the end of the 2nd block will assess similar measurements during a period of nicotine-product abstention.

 描述（由适用提供）：电子烟（EC）是尼古丁递送设备，可生成用户纳入的含尼古丁气溶胶。用户认为EC可用于帮助吸烟传统烟草（TC），并且与TC相比，不良健康影响的风险较低，在公共场所使用的可能性降低，成本降低以及缺乏与TC使用相关的有害粘附的气味。近年来，EC的使用急剧增长，目前估计是一个十亿美元的行业，拥有400多个现有品牌的EC和美国三家主要的美国烟草公司，现在销售自己的品牌。 FDA宣布了监管EC的意图。与FDA法规有关的关键问题包括EC的额外性和安全性。许多人认为，EC的功能与TC相同，并且EC被证明与TC一样添加剂，但情况可能并非如此，因为这些产品的设计和使用方法的根本差异。例如，我们假设与TC相比，EC的全身性尼古丁暴露将较低。尽管较低的尼古丁摄入量EC使用者将获得类似的奖励，而与TC相比，使用较高的戒断符号或渴望；而且，双重EC/ TC用户不会像高收益与低收益尼古丁TC的TC吸烟者一样滴定其尼古丁的日常摄入量。我们的建议特别关注与添加剂最密切相关的领域 EC的潜力，即：（1）EC作为尼古丁递送设备，涵盖了尼古丁摄入和药代动力学的问题，临时使用模式和尼古丁的滴定； （2）EC使用的主观影响，包括用于奖励，戒断和渴望的使用关系。我们还将检查EC使用安全性的各个方面（通过评估使用和生物标志物的心血管和马匹效应以及暴露于潜在有毒成分的生物标志物），并探讨对可能有助于区分EC与TC使用的生物标志物的识别和验证。研究对象将是TC和EC的双用户，因此我们可以比较受试者内部设计中经验丰富的用户的两种使用方式。这项研究将由两个1周的块（仅EC或仅TC条件）组成，其中4天的门诊AD额外的产品使用，然后在临床研究病房中进行3天，包括一次使用药代动力学研究，监测产品使用，受试者评估，血液和尿液收集，以评估生物标志物以及24小时的心脏疾病监测。在第二块块结束时，在尼古丁产物弃权期间的另外两天将评估类似的测量。