Pharmacokinetics And Pharmacodynamics Of Smoked Drugs Of Abuse

滥用吸食药物的药代动力学和药效学

基本信息

批准号：
8933807
负责人：
MARILYN A HUESTIS
金额：
$ 61.99万
依托单位：
NATIONAL INSTITUTE ON DRUG ABUSE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

A dramatic shift has occurred over the last decade in the route of administration of certain drugs of abuse in the United States. For example, the intravenous route for heroin has historically been the favored method of drug administration. This is changing with increased reports of intranasal and smoked administration of heroin. The reasons for these changes may include social and environmental factors such as the ease and convenience of smoking, avoidance of needle-transmitted diseases, and possible pharmacologic differences produced by the different routes of administration. In contrast to cocaine, tobacco (nicotine) and cannabis (tetrahydrocannabinol) have almost always been administered via smoking in the United States. The route of drug administration is a determinant of the toxicity and addictiveness of a given drug. The smoked route results in significant morbidity and mortality. Studies examine the influences exerted by routes of administration (intranasal, intravenous, and smoked) on pharmacokinetic parameters and drug-induced behavioral and physiologic effects of cocaine, methamphetamine, cannabis, heroin and nicotine. Physiological and behavioral measures are collected before and periodically after drug administration. Concurrent blood specimens are collected and analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry for drugs and metabolites. Behavioral measures of subjective effects and cognitive and psychomotor performance are evaluated by the different routes to compare magnitude of responses including measures of abuse liability. Investigation of plasma concentrations following administration of drugs by alternative routes permits determination of drug bioavailability, an important factor in route selection. Physiologic responses vary according to the speed, magnitude and duration of drug concentrations at the site of action. Intranasal administration was characterized by lower plasma concentrations and a slower onset of pharmacologic effects that were generally of lower magnitude than those observed by other routes of administration. These findings suggest that smoked cocaine ("crack") has a higher abuse liability and greater dependence-producing properties than equivalent doses of cocaine administered by the intravenous or intranasal route. Other studies found that liking scores were similar for smoked doses of heroin, cocaine, and nicotine. Together, these studies indicate that the smoked route of drug administration is associated with high levels of abuse liability and that a drug's abuse potential is not an inherent property of the drug, but can vary depending on how the drug is delivered.

过去十年中，美国某些滥用药物的给药途径发生了巨大的转变。例如，海洛因的静脉注射途径历来是最受欢迎的给药方法。随着鼻内和吸食海洛因的报道增多，这种情况正在发生变化。这些变化的原因可能包括社会和环境因素，例如吸烟的容易性和便利性、避免针头传播疾病以及不同给药途径可能产生的药理学差异。与可卡因相反，在美国，烟草（尼古丁）和大麻（四氢大麻酚）几乎总是通过吸烟来摄入。给药途径是给定药物的毒性和成瘾性的决定因素。熏制途径导致显着的发病率和死亡率。研究考察了给药途径（鼻内、静脉注射和吸烟）对可卡因、甲基苯丙胺、大麻、海洛因和尼古丁的药代动力学参数以及药物引起的行为和生理效应的影响。在给药之前和之后定期收集生理和行为测量数据。同时收集血液样本并通过气相色谱/质谱和液相色谱/质谱分析药物和代谢物。通过不同的途径评估主观效果以及认知和精神运动表现的行为测量，以比较反应的程度，包括滥用倾向的测量。通过替代途径给药后血浆浓度的研究可以确定药物的生物利用度，这是途径选择的一个重要因素。生理反应根据作用部位药物浓度的速度、强度和持续时间而变化。鼻内给药的特点是血浆浓度较低，药理作用起效较慢，其程度通常低于其他给药途径观察到的程度。这些发现表明，与通过静脉或鼻内途径施用的同等剂量的可卡因相比，吸食可卡因（“快克”）具有更高的滥用倾向和更大的依赖性产生特性。其他研究发现，人们对吸食海洛因、可卡因和尼古丁的喜好分数相似。总之，这些研究表明，烟熏给药途径与高水平的滥用倾向相关，并且药物的滥用潜力不是药物的固有特性，而是可能根据药物的输送方式而变化。