DETECTION OF DRUGS OF ABUSE IN HUMAN SALIVA

人类唾液中滥用药物的检测

• 批准号: 2449752
• 负责人: E J CONE
• 金额: --
• 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/2449752
• 关键词: blood chemistry; clinical research; diagnosis design /evaluation; dosage; drug abuse; drug administration routes; drug detection; drug metabolism; gas chromatography mass spectrometry; heroin; human subject; inhalation drug abuse; intravenous drug abuse; monitoring device; morphine; performance; pharmacokinetics; psychopharmacology; psychophysiology; pupillography; saliva; self medication

Despite the current popularity of smoking as a route of drug self- administration, there have been few human studies characterizing the pharmacokinetics and pharmacodynamics of smoked drugs of abuse. A variety of technological difficulties are encountered in the design of smoking studies, such as delivery of reproducible doses and limiting the amount of pyrolysis of parent drug. As part of a concerted research effort to deliver precise smoked doses of drug, a computer-assisted smoking device was utilized that delivered single puffs of heroin vapor to human subjects under controlled clinical conditions. Recovery studies indicated that the smoking device delivered approximately 89% of parent heroin to subjects. Although only two qualified heroin smokers could be identified as eligible volunteers, their participation provided the unique opportunity to study the pharmacokinetics and pharmacodynamics of smoked heroin. The two subjects were administered four smoked heroin doses in ascending order. In addition, four intravenous doses of heroin were administered for comparison of effects and estimation of bioavailability. Concurrent physiological, behavioral and performance measures were collected along with blood samples. Blood was analyzed for heroin, 6-acetylmorphine and morphine by solid phase extraction-gas chromatography/mass spectrometry. Heroin appeared rapidly in blood after administration, and peaked 1-5 min after smoking, similar to that observed following intravenous administration. Heroin concentrations declined rapidly to the limit of detection (1.0 ng/mL) by 30 min. 6- Acetylmorphine blood concentrations also peaked and declined rapidly after smoked heroin with peak concentrations occurring at 1-2 min after smoking. Morphine levels rose and decayed more slowly. Mean elimination half-lives for heroin, 6-acetylmorphine and morphine were 3.3 min, 5.4 min, and 18.8 min, respectively, by the smoked route. The bioavailability of smoked heroin was highly variable. Physiological measures such as pupil diameter demonstrated a counterclockwise hysteresis compared to heroin blood levels. The rapid onset of pharmacologic effects together with the early appearance of heroin and metabolites in blood following smoked heroin demonstrated the effectiveness of this route of drug administration. It is evident that the smoking route enables individuals to obtain similar pharmacologic effects as are produced by intravenous administration of heroin.

尽管目前吸烟作为一种自我吸毒的途径很受欢迎， 行政管理，很少有人类研究的特点， 吸烟药物滥用的药代动力学和药效学。 一 在设计中遇到了各种技术困难 吸烟研究，如提供可重复的剂量和限制 母体药物的热解量。 作为联合研究的一部分， 努力提供精确的吸烟剂量的药物，一个计算机辅助 使用了一种吸烟装置， 在受控的临床条件下对人类受试者进行治疗。 回收率研究 表明吸烟装置提供了大约89%的父母， 海洛因给受试者 虽然只有两个合格的海洛因吸食者可以 被确定为合格的志愿者，他们的参与提供了 研究药物动力学和药效学的独特机会 吸食海洛因 两名受试者被注射了四支吸食过的海洛因 剂量递增。 另外，四次静脉注射海洛因 进行比较，并估计 生物利用度 并发生理、行为和性能 测量值与血液样品一起收集沿着。 血液分析 固相萃取-气相色谱法测定海洛因、6-乙酰吗啡和吗啡 色谱/质谱法。 海洛因迅速出现在血液中， 给药后1-5 min达高峰，与给药前相似。 静脉给药后观察到。 海洛因浓度 在30 min内迅速下降至检测限（1.0 ng/mL）。6- 乙酰吗啡的血药浓度也达到峰值后迅速下降 吸海洛因后，峰浓度出现在吸海洛因后1-2分钟， smoking. 吗啡水平的上升和下降都比较缓慢。 平均消除 海洛因、6-乙酰吗啡和吗啡的半衰期分别为3.3min、5.4 熏烟法分别为18.8min和18.8min。 的 吸食海洛因的生物利用度变化很大。 生理 瞳孔直径等测量结果显示， 与海洛因血液浓度相比滞后。 的快速发作 药理作用加上海洛因的早期出现， 吸食海洛因后血液中的代谢物表明， 这种给药途径的有效性。 很明显 吸烟途径使个人获得类似的药理学 静脉注射海洛因所产生的效果。