Caffeine Disposition After Inhalation

描述(申请人提供)：能量饮料和酒精的共同滥用在年轻人中已经达到流行的程度。这种组合鼓励大量饮酒，并与酒精相关问题的增加有关，包括严重醉酒、暴力、性侵犯和酒后驾车。这种咖啡因和酒精的共同滥用恰逢能量饮料的引入，这预示着儿童和年轻人消费高咖啡因饮料，在能量饮料问世之前，他们对高咖啡因的接触有限。最近，一种新的吸入型咖啡因(Aeroshot TM)作为膳食补充剂被引入美国市场，它可能会使年轻人接触到更高水平的咖啡因，与酒精共滥用的风险甚至比能量饮料更大。AerohotTM是一种口红盒子大小和形状都很大的咖啡因输送装置。通过从试管的一端吸入含有100毫克咖啡因的细粉，将其沉积到口腔和上呼吸道。使用这种给药方法，咖啡因进入人体的量和速度尚不清楚。这些都是关键的问题，因为咖啡因在服用后的处置，特别是在关键的吸收阶段，是影响滥用潜力的重要因素。我们的总体假设是，与口服溶液相比，吸入咖啡因会导致更快的咖啡因吸收和更大的生理和行为影响。我们计划通过完成特定的目标来评估这一假说：1)确定咖啡因及其主要代谢物在口服溶液和吸入后的血药浓度-时间分布，以及特定的目标2)确定咖啡因在口服溶液和吸入后对心血管和情绪的影响。我们希望这项研究的结果将为单独使用AerohotTM设备以及与酒精联合使用提供重要的见解。我们的长期目标是确定咖啡因-酒精滥用的药效学，以及导致年轻人高风险饮酒的药代动力学因素。

DESCRIPTION (provided by applicant): The co-abuse of energy drinks with alcohol has reached epidemic levels in young adults. This combination encourages heavy binge alcohol use, and is associated with an increase in alcohol- related problems including severe intoxication, violence, sexual assault, and drunk driving. This co-abuse of caffeine and alcohol coincides with the introduction of energy drinks that heralded the consumption of high caffeine content beverages in children and young adults, who prior to the availability of energy drinks had limited exposure to high caffeine levels. Recently, a new inhaled form of caffeine (Aeroshot TM) was introduced into the U.S. market as a dietary supplement and could expose young adults to even higher levels of caffeine posing an even greater risk of co-abuse with alcohol than energy drinks. AeroshotTM is a caffeine delivery device the size and shape of a lipstick case. By inhaling from one end of the tube a fine powder containing 100 mg of caffeine is deposited into the oral cavity and upper airway. How much and how fast caffeine gets into the body using this method of administration are unknown. These are critical questions, because the disposition of caffeine following administration especially during the crucial absorption phase is an important factor influencing abuse potential. Our overall hypothesis is that caffeine administration by inhalation results in more rapid absorption of caffeine and greater physiologic and behavioral effects than administration by oral solution. We plan to evaluate this hypothesis by completing specific aim 1) determine the plasma concentration-time profile of caffeine and its major metabolites after administration by oral solution and inhalation, and specific aim 2) determine the cardiovascular and mood effects of caffeine after administration by oral solution and inhalation. We expect the results from this study to provide important insight into the abuse potential of the AeroshotTM device alone and in combination with alcohol. Our long term goal is to define the pharmacodynamics of caffeine- alcohol abuse and the pharmacokinetic factors contributing to high-risk alcohol use in young adults.