Boni J P, Barr W H, Martin B R
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
J Pharmacol Exp Ther. 1991 Apr;257(1):307-15.
Despite the great attention given to the pharmacological actions of cocaine in recent years, the mechanisms leading to acute intoxication and related deaths after cocaine smoking have not been fully elucidated. The present study was therefore undertaken to examine the pharmacokinetics and pharmacological effects of cocaine by the inhalation route. Cannulated, male Sprague-Dawley rats were exposed to a constant concentration of cocaine vapor (13.6 +/- 0.4 micrograms cocaine per ml mainstream air), during which time their biodispositional profile and cardiovascular responses were evaluated. The bioavailable doses of cocaine were 0.26 +/- 0.05 and 1.54 +/- 0.46 mg/kg, after 1.5- and 5.0-min exposures, respectively. Peak cocaine plasma concentrations of 95 +/- 26 and 205 +/- 58 ng/ml, for the 1.5- and 5.0-min exposures, respectively, occurred 1 min after the start of exposure. Increasing the duration of exposure significantly increased the bioavailability from 0.29 to 1.03 (P less than .05). Transient changes in heart rate and arterial blood pressure were generally dose-dependent and correlated temporally with peak cocaine plasma concentrations. During exposure, 70% of the animals demonstrated electrophysiological aberrations consistent with atrial arrhythmia and incomplete heart block. These findings suggest that a direct cardiotoxic effect resulted from inhalation of cocaine.
尽管近年来对可卡因的药理作用给予了极大关注，但吸食可卡因后导致急性中毒及相关死亡的机制尚未完全阐明。因此，本研究旨在通过吸入途径研究可卡因的药代动力学和药理作用。将雄性Sprague-Dawley大鼠插管，使其暴露于恒定浓度的可卡因蒸气中（每毫升主流空气中含13.6±0.4微克可卡因），在此期间评估其生物处置情况和心血管反应。暴露1.5分钟和5.0分钟后，可卡因的生物利用剂量分别为0.26±0.05和1.54±0.46毫克/千克。暴露开始1分钟后，1.5分钟和5.0分钟暴露组的可卡因血浆峰值浓度分别为95±26和205±58纳克/毫升。增加暴露时间可使生物利用度从0.29显著提高到1.03（P<0.05）。心率和动脉血压的短暂变化通常呈剂量依赖性，且在时间上与可卡因血浆峰值浓度相关。在暴露期间，70%的动物出现了与房性心律失常和不完全性心脏传导阻滞一致的电生理异常。这些发现表明，吸入可卡因会产生直接的心脏毒性作用。
