PHARMACODYNAMICS OF SMOKED DRUGS OF ABUSE

在过去十年中， 美国吸毒者服用可卡因。 青睐的 给药途径已从鼻内和静脉给药变更为给药 可卡因（“快克”）通过吸烟途径。 这种转变的原因 不太清楚，但可能包括社会和环境因素 例如吸烟路线的方便性，避免 针头传播疾病和可能的药理学差异 由不同的给药途径产生。 本研究旨在探讨 给药途径变化对 药代动力学参数和药物诱导的行为和生理 可卡因的影响。 6例提供知情同意书的男性受试者， 最近有通过静脉注射和烟熏途径使用可卡因的历史 参加了一项在一项研究中进行的盲法、双模拟、交叉研究， 临床研究病房 在不同的情况下，受试者接受单一 静脉注射可卡因（25 mg，盐酸可卡因）、鼻内注射可卡因（32 mg，盐酸可卡因）和烟熏（42 mg，可卡因碱）途径。 生理 行为测量在之前和之后定期收集 药品监督管理总局. 同时采集血液样本， 通过气相色谱/质谱法分析可卡因， 代谢物。 可卡因和苯甲酰芽子碱的血浆浓度为 通过非线性回归分析拟合药代动力学模型。 “良好”药物效果和“喜欢”的行为指标高于 吸烟途径比静脉途径，但生理变化， 与可卡因的血浆浓度大致相等。 鼻内可卡因给药的特点是较低的可卡因 血药浓度和药理作用起效较慢， 通常比其他路线观测到的要小 行政管理。 总的来说，这项研究表明，可卡因 通过烟熏途径给药产生了显著较高的 行为反应比同等剂量的可卡因 静脉注射途径。 这一发现表明，吸食可卡因 （“快克”）具有较高的滥用倾向和较大的依赖性， 比同等剂量的可卡因所管理的性能 静脉内或鼻内途径。

A dramatic shift has occurred over the last decade in the route of cocaine administration by drug abusers in the United States. The favored route has changed from intranasal and intravenous use to administration of cocaine ("crack") by the smoking route. The reasons for this shift are not well understood, but may include social and environmental factors such as the ease and convenience of the smoking route, avoidance of needle-transmitted disease, and possible pharmacologic differences produced by the different routes of administration. This study examined the influences exerted by changes in the route of administration on pharmacokinetic parameters and drug-induced behavioral and physiologic effects of cocaine. Six male subjects who provided informed consent and had a recent history of cocaine use by the intravenous and smoked routes participated in a blind, double-dummy, cross-over study conducted on a clinical research ward. On different occasions subjects received single doses of cocaine by the intravenous (25 mg, cocaine HCl), intranasal (32 mg, cocaine HCl) and smoked (42 mg, cocaine base) routes. Physiologic and behavioral measures were collected prior to and periodically after drug administration. Concurrent blood samples were collected and analyzed by gas chromatography/mass spectrometry for cocaine and metabolites. Plasma concentrations of cocaine and benzoylecgonine were fitted to pharmacokinetic models by non-linear regression analysis. Behavioral measures of "good" drug effects and "liking" were higher by the smoked route than the intravenous route, but physiologic changes were approximately equal at equivalent plasma concentrations of cocaine. Intranasal cocaine administration was characterized by lower cocaine plasma concentrations and a slower onset of pharmacologic effects that were generally of lesser magnitude than those observed by other routes of administration. Overall, this study demonstrated that cocaine administration by the smoked route produced substantially higher behavioral responses than an equivalent dose of cocaine administered by the intravenous route. This finding suggests 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.