Effect of dose on the pharmacokinetics of intravenous nicotine in the rat.
Effect of dose on the pharmacokinetics of intravenous nicotine in the rat.
复制标题
剂量对大鼠静脉注射尼古丁药代动力学的影响。
DOI：
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发表时间：
1977
影响因子：
3.9
通讯作者：
J. Adir
中科院分区：
文献类型：
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作者：
R. Miller;K. Rotenberg;J. Adir
在雄性Fischer-344大鼠中评价了静脉注射0.08、0.4或0.8 mg/kg剂量后[甲基-14C]尼古丁的药代动力学。尼古丁浓度呈双指数下降，平均半衰期为0.92 - 1.10小时，与剂量无关，但尼古丁的总血浆清除率增加（p小于0.05）从0.08 mg/kg剂量的平均值2.53升/小时-kg降至0.4和0.8 mg/kg剂量的平均值3.88和4.04，分别主要代谢产物可替宁的形成半衰期（范围0.33-0.46 h）或消除半衰期（范围5.39-6.63 h）无剂量相关差异。然而，可替宁血药浓度-时间曲线下面积并未随尼古丁剂量成比例增加，表明尼古丁总血浆清除率的剂量相关性增加并非由于其向可替宁的生物转化增加。关于尼古丁的其他极性代谢产物的处置动力学，获得了类似的结论。尼古丁及其代谢产物的尿液排泄量与剂量无关。
The pharmacokinetics of [methyl-14C]nicotine were evaluated in male Fischer-344 rats following the iv injection of 0.08-, 0.4-, or 0.8-mg/kg doses. Independent of dose, the concentration of nicotine declined biexponentially with a mean half-life ranging from 0.92 to 1.10 hr. However, the total plasma clearance of nicotine increased (p less than 0.05) from a mean value of 2.53 liter/hr-kg at the 0.08 mg/kg dose to mean values of 3.88 and 4.04 at the 0.4- and 0.8-mg/kg doses, respectively. There were no dose-related differences in the half-life of formation of the major metabolite, cotinine (range 0.33-0.46 hr) or the half-life of its elimination (range 5.39-6.63 hr). However, the areas under the cotinine plasma concentration-time curves did not increase proportionately with the dose of nicotine, indicating that the dose-related increase in the total plasma clearance of nicotine is not due to an increase in its biotransformation to cotinine. Similar conclusions were obtained with regard to the disposition kinetics of other polar metabolites of nicotine. The urinary excretions of nicotine and its metabolites were dose-independent.