PHARMACODYNAMICS OF SMOKED DRUGS OF ABUSE

在过去的十年中，发生了戏剧性的转变 美国吸毒者对可卡因的管理。最受欢迎的 给药途径已从鼻腔和静脉给药改为给药 可卡因(“可卡因”)的吸食路线。这一转变的原因 没有被很好地理解，但可能包括社会和环境因素 如吸烟路线的便利和方便，避免 针传疾病，以及可能的药理差异 由不同的给药途径产生。这项研究检查了 执政方式的变化对我国的影响 药代动力学参数与药物诱导的行为和生理 可卡因的影响。六名男性受试者提供知情同意并 最近有通过静脉和吸烟途径使用可卡因的历史 参与了一项盲目、双模拟、交叉研究，研究对象为 临床研究病房。在不同的场合，受试者只接受一次 静脉注射可卡因剂量(25毫克，盐酸可卡因)，鼻腔注射(32 可卡因(盐酸)和烟熏(42毫克，可卡因)路线。生理学 并在之前和之后定期收集行为测量数据 药品管理局。同时采集血液样本，并 用气相色谱/质谱仪分析可卡因和 代谢物。血浆中可卡因和苯甲酰ecGonine的浓度是 用非线性回归分析拟合药动学模型。 行为测量的“良好”的药物效果和“喜欢”更高的 烟雾化途径优于静脉途径，但生理变化 相当于同等血浆浓度的可卡因。 鼻腔注射可卡因的特点是可卡因含量较低 血浆浓度和较慢的药理作用 通常比其他路线观测到的震级要小 行政管理部门。总体而言，这项研究表明可卡因 通过烟熏路线服用会产生显著更高的 行为反应比同等剂量的可卡因给药 静脉注射。这一发现表明，吸烟的可卡因 (“可卡因”)有更高的滥用倾向和更大的依赖产生 特性比同等剂量的可卡因由 静脉或鼻腔途径。

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.