METABOLISM OF NICOTINE TO COTININE STUDIED BY A DUAL STABLE-ISOTOPE METHOD
METABOLISM OF NICOTINE TO COTININE STUDIED BY A DUAL STABLE-ISOTOPE METHOD
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DOI：
10.1038/clpt.1994.169
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发表时间：
1994-11-01
影响因子：
6.7
通讯作者：
JACOB, P
中科院分区：
文献类型：
--
作者：
BENOWITZ, NL;JACOB, P
目的：（1）确定尼古丁和可替宁的处置动力学，包括尼古丁转化为可替宁的分数，（2）比较氘标记和未标记的可替宁的处置动力学，（3）开发一种基于药代动力学的方法，用于估计吸烟引起的尼古丁每日摄入量。20名吸烟者接受了氘标记尼古丁（d（2））和可替宁（d（4））的联合输注。6名非吸烟者接受了未标记的可替宁、可替宁-d（2）和可替宁-d（4）的联合输注。每日摄入的尼古丁估计与使用的血浆可替宁浓度在随意吸烟，清除标记的可替宁，和分数转换尼古丁可替nine.Results：标记与未标记的可替宁和可替宁在吸烟者与非吸烟者的动力学是相似的。平均而言，72%的尼古丁转化为可替宁，范围从55%到92%。尼古丁清除率较低的受试者尼古丁向可替宁的转化分数较低，表明这是尼古丁最快速的近端代谢途径。估计吸烟引起的每日尼古丁摄入量的方程为：D-nic（mg/24 hr）= K x（血浆Cot）（ng/ml），其中K平均值为0.08，范围为0.047至0.102。可替宁清除率的个体变异性（变异系数，27.5%）比尼古丁转化为可替宁分数的变异性更能解释K的变异性（变异系数为12.3%）。我们的研究提供了关于C-尼古丁氧化为可替宁，以及使用血浆可替宁作为烟草尼古丁每日摄入量指标的定量观点。
Objectives: (1) To determine the disposition kinetics of nicotine and cotinine, including the fractional conversion of nicotine to cotinine, (2) to compare the disposition kinetics of deuterium-labeled and unlabeled cotinine, and (3) to develop a pharmacokinetically based method for estimating daily intake of nicotine from cigarette smoking.Study design: Twenty cigarette smokers received a combined infusion of deuterium-labeled nicotine (d(2)) and cotinine (d(4)). Six nonsmokers received a combined infusion of unlabeled cotinine, cotinine-d(2) and cotinine-d(4). Daily intake of nicotine was estimated with use of the plasma cotinine concentration during ad libitum smoking, clearance of labeled cotinine, and fractional conversion of nicotine to cotinine.Results: The kinetics of labeled versus unlabeled cotinine and of cotinine in smokers versus nonsmokers were similar. On average, 72% of nicotine was converted to cotinine, with a range from 55% to 92%. Subjects with lower clearances of nicotine had lower fractional conversion of nicotine to cotinine, indicating that this is the most rapid of the proximate metabolic pathways for nicotine. The equation for estimating daily intake of nicotine from smoking was: D-nic (mg/24 hr) = K x (Plasma Cot) (ng/ml), where K averaged 0.08, with a range from 0.047 to 0.102. Individual variability in the clearance of cotinine (coefficient of variation, 27.5%) accounts for more of the variability in K than does variability in the fractional conversion of nicotine to cotinine (coefficient of variation, 12.3%).Conclusions: Our study provides quantitative data on individual variability in the extent of C-oxidation of nicotine to cotinine and a quantitative perspective on the use of plasma cotinine as an indicator of daily intake of nicotine from tobacco.