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

来源：
https://reporter.nih.gov/project-details/8933807
关键词：
Appearance Behavioral Biological Availability Blood specimen Cannabis Cocaine Cognitive Crack Cocaine Dependence Disease Dose Drug Administration Routes Drug Kinetics Environmental Risk Factor Excretory function Goals Hair Heroin Intranasal Administration Intravenous Investigation Liquid substance Mass Fragmentography Measures Metabolism Methamphetamine Methods Morbidity - disease rate Needles Nicotine Oral Pharmaceutical Preparations Pharmacodynamics Physiological Plasma Property Psychomotor Performance Reporting Route Site Smoke Smoking Speed Sweat Sweating Tetrahydrocannabinol Time Tobacco Toxic effect United States Urine Whole Blood absorption behavior measurement drug of abuse liquid chromatography mass spectrometry mortality response social

Appearance Behavioral Biological Availability Blood specimen Cannabis Cocaine Cognitive Crack Cocaine Dependence Disease Dose Drug Administration Routes Drug Kinetics Environmental Risk Factor Excretory function Goals Hair Heroin Intranasal Administration Intravenous Investigation Liquid substance Mass Fragmentography Measures Metabolism Methamphetamine Methods Morbidity - disease rate Needles Nicotine Oral Pharmaceutical Preparations Pharmacodynamics Physiological Plasma Property Psychomotor Performance Reporting Route Site Smoke Smoking Speed Sweat Sweating Tetrahydrocannabinol Time Tobacco Toxic effect United States Urine Whole Blood absorption behavior measurement drug of abuse liquid chromatography mass spectrometry mortality response social

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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.

在过去的十年中，在美国某些虐待药物的管理途径中发生了巨大的转变。例如，海洛因的静脉注射途径历史上一直是药物管理的最受欢迎的方法。随着鼻内和熏制的海洛因给药的报道，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，例如吸烟的轻松和便利性，避免针刺疾病的疾病以及不同行政途径产生的可能的药理差异。与可卡因，烟草（尼古丁）和大麻（四氢大麻酚）相反，在美国，几乎总是通过吸烟来施用。药物管理途径是给定药物的毒性和成瘾性的决定因素。烟熏路线会导致明显的发病率和死亡率。研究研究了可卡因，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诱导的行为和生理影响的药代动力学参数以及药物诱导的行为和生理影响的影响。在药物给药之前和定期收集生理和行为措施。通过气相色谱/质谱法和药物和代谢物的液相色谱/质谱法收集并分析并发的血样。主观效应以及认知和精神运动表现的行为度量通过不同的途径进行评估，以比较响应的大小，包括滥用责任的措施。通过替代途径施用药物后血浆浓度的研究允许确定药物生物利用度，这是途径选择的重要因素。生理反应根据作用部位的药物浓度的速度，幅度和持续时间而变化。鼻内给药的特征是血浆浓度较低和药理学作用发作较慢，通常比其他给药途径观察到的幅度低。这些发现表明，烟熏可卡因（“裂纹”）具有更高的滥用责任和更大的产生依赖性特性，而不是同等剂量的可卡因。其他研究发现，喜欢分数的海洛因，可卡因和尼古丁的烟熏分数相似。总之，这些研究表明，熏制药物管理途径与高水平的滥用责任有关，并且药物的滥用潜力不是药物的固有特性，而是根据该药物的递送而有所不同。