Baker Jennifer, Jatlow Peter, Pade Patricia, Ramakrishnan Viswanathan, McCance-Katz Elinore F
Virginia Commonwealth University, Richmond, Virginia, USA.
Am J Drug Alcohol Abuse. 2007;33(4):619-25. doi: 10.1080/00952990701407694.
We report results of a randomized, double-blind, placebo-controlled, within-subject study (n = 8) to determine the ability of cocaethylene to modulate acute responses to cocaine and identify significant pharmacokinetic interactions between cocaine and cocaethylene. Stable plasma cocaethylene concentrations (0, 50, or 200 ng/ml) were maintained for 840 minutes. Cocaine (0, 0.25, or 0.5 mg/kg) was injected over 1 minute after 240 minutes of cocaethylene. Blood samples, subjective, and physiological measures were collected. No differences over baseline responses were observed following 240 minutes of a steady state cocaethylene infusion for cardiovascular or subjective responses. "Rush" duration following a cocaine challenge (0.5 mg/kg) declined when administered during the course of a 200 ng/mL cocaethylene infusion. (p = 0.01). No pharmacokinetic interaction occurred when cocaine was administered in conjunction with cocaethylene. Findings indicate that continuous 8-hour exposure to cocaethylene is safe, produces acute tolerance to itself, and reduces some behavioral effects of coadministered cocaine. Agonist substitution therapy may have potential as an alternative treatment for cocaine dependence.
我们报告了一项随机、双盲、安慰剂对照的自身对照研究（n = 8）的结果，以确定可卡因乙烯基醚调节对可卡因急性反应的能力，并确定可卡因与可卡因乙烯基醚之间显著的药代动力学相互作用。稳定的血浆可卡因乙烯基醚浓度（0、50或200 ng/ml）维持840分钟。在可卡因乙烯基醚输注240分钟后，在1分钟内注射可卡因（0、0.25或0.5 mg/kg）。采集血样、主观和生理指标。在可卡因乙烯基醚稳定输注240分钟后，心血管或主观反应方面未观察到与基线反应的差异。在200 ng/mL可卡因乙烯基醚输注过程中给予可卡因挑战（0.5 mg/kg）时，“冲动”持续时间缩短（p = 0.01）。可卡因与可卡因乙烯基醚联合给药时未发生药代动力学相互作用。研究结果表明，连续8小时暴露于可卡因乙烯基醚是安全的，会产生自身急性耐受性，并降低联合使用可卡因的一些行为效应。激动剂替代疗法可能有潜力作为可卡因依赖的替代治疗方法。
