Correlation between pharmacological effects and plasma cocaine concentrations after smoked administration
Correlation between pharmacological effects and plasma cocaine concentrations after smoked administration
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DOI：
10.1093/jat/26.7.382
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发表时间：
2002-10-01
影响因子：
2.5
通讯作者：
Cone, EJ
中科院分区：
文献类型：
--
作者：
Jenkins, AJ;Keenan, RM;Cone, EJ
血液可卡因浓度与药理作用之间的关系具有理论和实际意义。这项研究利用计算机辅助吸烟装置向7名人类志愿者提供三种活性剂量（10,20和40mg）的可卡因碱。以递增剂量设计给药，随机放置安慰剂。生理、主观和表现指标与血液样本同时采集。血浆可卡因浓度的平均峰值在20毫克和40毫克剂量后2分钟和10毫克剂量后5分钟达到。在收缩压和舒张压、“感觉”、“好”药和“喜欢”药的主观效应方面也均在给药后立即达到最大反应。在给药后不久，瞳孔直径和心率的增加表现出与血浆可卡因浓度有关的适度逆时针滞后。收缩压和舒张压、心率以及一些药物效应的主观和性能指标显示，吸食可卡因后存在双相反应。最初高于基线水平，随后在吸食可卡因后的一段时间内明显代偿性下降至基线水平以下。尽管有证据表明某些措施存在滞后和双相反应，但在给药后4小时内，平均血浆可卡因浓度与几种药理作用之间存在线性相关。在可卡因浓度可检测到的情况下，若干主观和心血管指标恢复到基线水平。
The relationship between blood cocaine concentrations and pharmacological effects is of both theoretical and practical interest. This study utilized a computer-assisted smoking device for the delivery of three active doses (10, 20, and 40 mg) of cocaine base to seven human volunteers. Doses were administered in an ascending dose design with random placement of placebo. Physiological, subjective, and performance measures were collected concurrently with blood samples. Mean peak plasma cocaine concentrations were achieved at 2 min after the 20-mg and 40-mg doses and at 5 rain after the 10-mg dose. Maximal responses in systolic and diastolic blood pressure, “feel”, “good” drug, and drug “liking” subjective effects were also achieved immediately after drug administration. Pupil diameter and heart rate increases demonstrated a modest counter-clockwise hysteresis in relation to plasma cocaine concentrations shortly after dosing. Systolic and diastolic blood pressure, heart rate, and some subjective and performance measures of drug effect demonstrated a biphasic response after smoked cocaine. Initial increases above baseline levels were followed by an apparent compensatory decrease below baseline levels at a later time after smoked cocaine. Despite evidence of hysteresis and biphasic responses for some measures, linear correlation was obtained between mean plasma cocaine concentrations and several pharmacological effects over a period of 4 h after dosing. Several subjective and cardiovascular measures returned to baseline levels in the presence of detectable concentrations of cocaine.