Division of Clinical Pharmacology, Department of Medicine, University of California, San Francisco, CA.
Center for Tobacco Control Research and Education, Department of Medicine, University of California, San Francisco, CA.
Nicotine Tob Res. 2020 Feb 6;22(2):288-292. doi: 10.1093/ntr/ntz034.
Accurate measurement of nicotine exposure from cigarette smoke is important in studying disease risk and level of dependence. Urine total nicotine equivalents, the molar sum of nicotine and six metabolites (NE7), accounts for more than 90% of a nicotine dose and is independent of individual metabolic differences. However, measuring NE7 is technically difficult and costly. We compared NE7, the gold standard of nicotine intake, with different combinations of fewer urinary nicotine metabolites. We also examined the impact of individual differences in nicotine metabolic rate, sex, and race on strength of association with NE7.
Urine samples from 796 daily smokers, who participated across five clinical studies, were assayed for nicotine and/or metabolites. Associations with NE7 were assessed by regression and Bland-Altman analyses.
RESULTS: Overall, the molar sum of urine [cotinine + 3'-hydroxycotinine (3HC)] (NE2) and [nicotine + cotinine + 3HC] (NE3) were strongly correlated with NE7 (r = .97 and .99, respectively). However, in slow metabolizers NE2 was less predictive of NE7, whereas NE3 was equally robust. Urine total cotinine was also strongly correlated with NE7 (r = .87).
Urine NE3 is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, whereas NE2 is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies.
The molar sum of urine total nicotine, cotinine and 3HC (NE3) is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, and performs as well as measuring seven nicotine metabolites (NE7). The sum of cotinine and 3HC (NE2) is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies.
准确测量香烟烟雾中的尼古丁暴露量对于研究疾病风险和依赖程度非常重要。尿中总尼古丁当量(尼古丁和六种代谢物的摩尔总和,NE7)占尼古丁剂量的 90%以上,且不受个体代谢差异的影响。然而,测量 NE7 在技术上具有难度并且成本高昂。我们比较了 NE7(尼古丁摄入量的金标准)与较少的尿尼古丁代谢物的不同组合。我们还研究了尼古丁代谢率、性别和种族等个体差异对与 NE7 关联强度的影响。
796 名参与五项临床研究的每日吸烟者的尿液样本进行了尼古丁和/或代谢物的检测。通过回归和 Bland-Altman 分析评估与 NE7 的相关性。
总体而言,尿中 [可替宁+3'-羟基可替宁(3HC)](NE2)和 [尼古丁+可替宁+3HC](NE3)的摩尔总和与 NE7 呈强相关(r 分别为.97 和.99)。然而,在代谢较慢的个体中,NE2 对 NE7 的预测性较差,而 NE3 则同样可靠。尿中总可替宁与 NE7 也呈强相关(r=.87)。
尿中 NE3 是每日尼古丁摄入量的可靠生物标志物,独立于个体代谢差异,而在代谢较慢的个体中,NE2 则不太准确。我们的发现为评估烟草研究中尼古丁暴露的更严格和更具成本效益的测量方法的选择提供了信息。
尿中总尼古丁、可替宁和 3HC 的摩尔总和(NE3)是每日尼古丁摄入量的可靠生物标志物,独立于个体代谢差异,与测量七种尼古丁代谢物(NE7)的效果相当。在代谢较慢的个体中,可替宁和 3HC 的总和(NE2)不太准确。我们的发现为评估烟草研究中尼古丁暴露的更严格和更具成本效益的测量方法的选择提供了信息。