Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan.
Int J Environ Res Public Health. 2010 Jul;7(7):2953-64. doi: 10.3390/ijerph7072953. Epub 2010 Jul 20.
Human biomonitoring of plasma and urinary levels of nicotine, cotinine, and 3'-hydroxycotinine was conducted after daily cigarette smoking in a population of 92 male Japanese smokers with a mean age of 37 years who had smoked an average of 23 cigarettes per day for 16 years. Members of the population were genotyped for the nicotine-metabolizing enzyme cytochrome P450 2A6 (CYP2A6). The mean levels of nicotine, the levels of its metabolites cotinine and 3'-hydroxycotinine, and the sum of these three levels in subjects one hour after smoking the first cigarette on the sampling day were 20.1, 158, 27.7, and 198 ng/mL in plasma and 846, 1,020, 1,010, and 2,870 ng/mL in urine under daily smoking conditions. Plasma levels of 3'-hydroxycotinine and urinary levels of nicotine and 3'-hydroxycotinine were dependent on the CYP2A6 phenotype group, which was estimated from the CYP2A6 genotypes of the subjects, including those with whole gene deletion. Plasma cotinine levels were significantly correlated with the number of cigarettes smoked on the day before sampling (r = 0.71), the average number of cigarettes smoked daily (r = 0.58), and the Brinkman index (daily cigarettes x years, r = 0.48) under the present conditions. The sum of nicotine, cotinine, and 3'-hydroxycotinine concentrations in plasma showed a similar relationship to that of the plasma cotinine levels. Urinary concentrations of cotinine and the sum of nicotine metabolite concentrations also showed significant correlations with the plasma levels and the previous day's and average cigarette consumption. The numbers of cigarettes smoked per day by two subjects with self-reported light smoking habits were predicted by measuring the urinary cotinine concentrations and using linear regression equations derived from above-mentioned data. These results indicate that biomonitoring of the urinary cotinine concentration is a good, easy-to-use marker for plasma levels of cotinine and the sum of nicotine metabolites in smokers independent of genetic polymorphism of CYP2A6.
对 92 名平均年龄 37 岁、平均每天吸烟 23 支、吸烟 16 年的日本男性吸烟者进行了人体生物监测，以监测血浆和尿液中尼古丁、可替宁和 3'-羟基可替宁的水平。人群中的成员进行了尼古丁代谢酶细胞色素 P450 2A6（CYP2A6）的基因分型。在每日吸烟条件下，受试者在采样日第一支香烟后一小时，血浆中尼古丁、其代谢物可替宁和 3'-羟基可替宁的水平以及这三种水平的总和分别为 20.1、158、27.7 和 198ng/ml，尿液中尼古丁和 3'-羟基可替宁的水平分别为 846、1020、1010 和 2870ng/ml。血浆 3'-羟基可替宁水平和尿液中尼古丁和 3'-羟基可替宁水平依赖于 CYP2A6 表型组，该组由受试者的 CYP2A6 基因型估计，包括那些具有全基因缺失的受试者。在目前的条件下，血浆可替宁水平与前一天吸烟量（r = 0.71）、平均每日吸烟量（r = 0.58）和布利克曼指数（每日吸烟量 x 年，r = 0.48）显著相关。在目前的条件下，血浆中尼古丁、可替宁和 3'-羟基可替宁浓度的总和与血浆可替宁水平表现出相似的关系。尿液中可替宁和尼古丁代谢物浓度的总和也与血浆水平以及前一天和平均吸烟量显著相关。通过测量尿中可替宁浓度并使用从上述数据推导出来的线性回归方程，预测了两位自报吸烟量较少的受试者的每日吸烟量。这些结果表明，生物监测尿中可替宁浓度是一种简单易用的标志物，可用于监测吸烟者血浆中可替宁水平和尼古丁代谢物的总和，而不受 CYP2A6 遗传多态性的影响。
