Elimination kinetics of the tobacco-specific biomarker and lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
Elimination kinetics of the tobacco-specific biomarker and lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
复制标题
DOI：
10.1158/1055-9965.epi-09-0874
复制
发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Benowitz NL
中科院分区：
文献类型：
--
作者：
Goniewicz ML;Havel CM;Peng MW;Jacob P 3rd;Dempsey D;Yu L;Zielinska-Danch W;Koszowski B;Czogala J;Sobczak A;Benowitz NL
4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）是烟草特异性的，并且具有比迄今为止研究的其他烟草生物标志物更长的半衰期。NNAL半衰期的准确测量对于评估烟草烟雾暴露的最佳使用非常重要。我们确定了NNAL在临床研究病房的8名每日吸烟者和现实生活环境中的5名偶尔吸烟者尿液中的半衰期。每天吸烟者在戒烟后监测14天，偶尔吸烟者监测60天。使用二房室模型，每日吸烟者组终末相的平均半衰期为10.3天（β相），使用非房室模型，为9.1天。在偶发组中，这些值分别为17.6和16.0天。两组的α相半衰期分别为14.3和27.8小时。NNAL终末半衰期的受试者间变异系数范围为14%-30%，受试者内变异系数范围为3%-18%。两例受试者的血浆和尿液半衰期与血浆分析结果非常一致：7.4 vs 7.9天和9.2 vs 10.7天。NNAL的平均肾脏清除率为13 ± 2.3 mL/min。NNAL的终末半衰期为10至18天，表明该生物标志物可用于检测停止暴露后6至12周的烟草烟雾暴露，并需要类似的时间来评估从一种烟草产品转换为另一种烟草产品后NNAL的稳定水平。
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is tobacco specific and has a longer half-life than other tobacco biomarkers studied thus far. An accurate measurement of the NNAL half-life is important for optimal use to assess exposure to tobacco smoke. We determined the half-life of NNAL in urine in eight daily smokers on a clinical research ward and in five occasional smokers in a real-life environment. Total NNAL in urine was monitored for 14 days in daily smokers after stopping smoking and for up to 60 days in occasional smokers. The average half-life for the terminal phase in the daily smoker group using a two-compartmental body model was 10.3 days (beta phase), and using a noncompartmental model, it was 9.1 days. In the occasional group, these values were 17.6 and 16.0 days, respectively. The alpha-phase half-lives were 14.3 and 27.8 hours for the two groups, respectively. The inter-subject coefficient of variation of the NNAL terminal half-life ranged from 14% to 30%, and the intra-subject coefficient of variation ranged from 3% to 18%. There was very good agreement between the plasma and urinary half-lives in two subjects with plasma analyses: 7.4 versus 7.9 days and 9.2 versus 10.7 days. Mean renal clearance of NNAL was 13 ± 2.3 mL/min. The terminal half-life of NNAL of 10 to 18 days indicates that this biomarker can be used to detect tobacco smoke exposure for 6 to 12 weeks after cessation of exposure and requires a similar time to assess the steady levels of NNAL after switching from one tobacco product to another.