Adir J, Wildfeuer W, Miller R P
J Pharmacol Exp Ther. 1980 Feb;212(2):274-9.
The pharmacokinetics of nicotine was compared in male Fischer-344 rats pretreated with an ethanol or a sucrose solution for 12.5 days. The animals received either ethanol at doses of 4 g/kg/day for 7 days followed by 8 g/kg/day for 5.5 days or daily doses of an isocaloric-isovolumetric sucrose solution for 12.5 days by gastric intubation. On the fourteenth day, a 0.4 mg/kg dose of [methyl-14C]nicotine was injected i.v. to both groups, and blood samples were collected at timed intervals for 30 hr. Nicotinine and its metabolites in plasma were separated by thin-layer chromatography and quantitated by liquid scintillation counting. The plasma levels of total radioactivity, nicotine, cotinine and other polar metabolites were significantly lower in the ethanol as compared to the sucrose-treated rats. Ethanol pretreatment produced no changes in the hybrid rate constants describing the biphasic decline of plasma nicotine concentration but its apparent volume of distribution and total plasma clearance were increased by 45% (P less than .05) suggesting that ethanol may alter the distribution of nicotine. The apparent volume of distribution of cotinine and its rate of production also were significantly increased indicating an ethanol-related induction of this major metabolite of nicotine.
在经乙醇或蔗糖溶液预处理12.5天的雄性Fischer-344大鼠中比较了尼古丁的药代动力学。动物通过胃内插管接受以下处理：连续7天给予4 g/kg/天的乙醇，随后5.5天给予8 g/kg/天的乙醇；或连续12.5天给予等热量等体积的蔗糖溶液。在第14天，两组均静脉注射0.4 mg/kg剂量的[甲基-14C]尼古丁，并在30小时内定时采集血样。血浆中的尼古丁及其代谢产物通过薄层色谱法分离，并用液体闪烁计数法定量。与蔗糖处理的大鼠相比，乙醇处理组大鼠血浆中总放射性、尼古丁、可替宁和其他极性代谢产物的水平显著降低。乙醇预处理并未改变描述血浆尼古丁浓度双相下降的混合速率常数，但其表观分布容积和总血浆清除率增加了45%（P<0.05），这表明乙醇可能会改变尼古丁的分布。可替宁的表观分布容积及其生成速率也显著增加，表明乙醇可诱导尼古丁的这种主要代谢产物。
