Pharmacokinetics And Pharmacodynamics Of Drugs Of Abuse

滥用药物的药代动力学和药效学

• 批准号: 7593259
• 负责人: Marilyn Huestis
• 金额: $ 21万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 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/7593259
• 关键词: Appearance; Biological; Blood; Brain; Cannabis; Cannabis Smoking; Clinical Research; Cocaine; Codeine; Cognitive; Data Analyses; Drug Administration Routes; Drug Kinetics; Functional Magnetic Resonance Imaging; Gas Chromatography; Hair; Heroin; Insufflation; Intravenous; Liquid substance; Mass Chromatography; Measures; Methamphetamine; Neuraxis; Oral; Oral Administration; Pharmaceutical Preparations; Pharmacodynamics; Phase; Physiological; Plasma; Psychomotor Performance; Route; Site; Skin; Smoke; Solid; Spectrometry; Speed; Staging; Sweat; Sweating; Tissues; Urine; drug of abuse; intravenous administration; liquid chromatography mass spectrometry; receptor

There are many factors that influence the addictiveness of a drug. The route of administration is a major determinant of the speed of drug entry into the body and to receptors in the central nervous system. Clinical studies are in progress which determine the importance of different routes of administration and the relationship of blood concentrations of drug and active metabolites to concomitant drug effects. Studies of heroin, cocaine, methamphetamine, codeine and cannabis administration by the intravenous, smoked, intranasal and oral routes are underway or in the data analysis stage. Pharmacodynamic effects include subjective, cognitive and psychomotor performance, physiological measures and specific brain activity as assessed by fMRI. Plasma, urine, oral fluid, sweat, hair and skin are analyzed for drug and metabolites by solid phase extraction-gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. The intravenous and smoked routes produce a rapid onset of pharmacological effects together with an early appearance of drug and metabolites in blood. Evidence of delays in distribution to effector sites are observed following cannabis smoking, but drug effects following heroin and cocaine administration coincided more closely with concurrent blood concentrations. Onset of effects is delayed following intranasal and especially after oral administration.

有许多因素会影响药物的成瘾性。给药途径是药物进入体内和进入中枢神经系统受体的速度的主要决定因素。 正在进行临床研究，以确定不同给药途径的重要性以及药物和活性代谢物的血药浓度与伴随药物效应的关系。关于通过静脉注射、烟熏、鼻内和口服途径给予海洛因、可卡因、甲基苯丙胺、可待因和大麻的研究正在进行或处于数据分析阶段。 药效学作用包括通过fMRI评估的主观、认知和精神运动表现、生理指标和特定大脑活动。通过固相萃取-气相色谱/质谱法和液相色谱/质谱法分析血浆、尿液、口腔液、汗液、毛发和皮肤中的药物和代谢物。 静脉注射和烟熏途径产生快速起效的药理作用，同时药物和代谢物在血液中较早出现。在吸食大麻后观察到延迟分布到效应部位的证据，但海洛因和可卡因给药后的药物效应与同时发生的血液浓度更密切地吻合。鼻内给药后，尤其是口服给药后，起效延迟。