Yuki Dai, Kikuchi Akira, Miura Naoki, Kakehi Aoi, Onozawa Masahiro
Product Science Division, R&D Group, Japan Tobacco Inc., Yokohama, Kanagawa, Japan.
Regul Toxicol Pharmacol. 2013 Nov;67(2):240-5. doi: 10.1016/j.yrtph.2013.08.002. Epub 2013 Aug 8.
This study investigated the relationship between plasma and saliva cotinine kinetics after smoking one cigarette and the relationship between cotinine kinetics and estimated nicotine intake, which was calculated as mouth level exposure (MLE) of nicotine, from smoking two test cigarettes with different nicotine yields. This study was conducted in 16 healthy adult Japanese smokers, who did not have null nor reduced-activity alleles of CYP2A6, with a quasi-randomized crossover design of smoking a low-tar cigarette or a high-tar cigarette. Saliva cotinine showed similar concentration profiles to plasma cotinine, and all of the calculated pharmacokinetic parameters of cotinine showed the same values in plasma and saliva. The Cmax and AUC of cotinine showed almost the same dose-responsiveness to the estimated MLE of nicotine between plasma and saliva, but the tmax and t1/2 of cotinine were not affected by the estimated MLE of nicotine in either plasma or saliva. The results show that saliva cotinine kinetics reflects plasma cotinine kinetics, and measurement of saliva cotinine concentration gives the same information as plasma cotinine on the nicotine intake. Thus, saliva cotinine would be a good and less-invasive exposure marker of cigarette smoke, reflecting the plasma cotinine concentration and kinetics.
本研究调查了吸一支烟后血浆和唾液中可替宁动力学之间的关系，以及可替宁动力学与估计的尼古丁摄入量之间的关系，后者通过吸两支尼古丁含量不同的测试香烟的口腔水平暴露（MLE）来计算。本研究在16名健康的成年日本吸烟者中进行，这些吸烟者没有CYP2A6的无效或低活性等位基因，采用吸低焦油香烟或高焦油香烟的准随机交叉设计。唾液可替宁显示出与血浆可替宁相似的浓度曲线，并且所有计算出的可替宁药代动力学参数在血浆和唾液中显示出相同的值。可替宁的Cmax和AUC在血浆和唾液中对估计的尼古丁MLE显示出几乎相同的剂量反应性，但可替宁的tmax和t1/2在血浆或唾液中均不受估计的尼古丁MLE的影响。结果表明，唾液可替宁动力学反映了血浆可替宁动力学，并且唾液可替宁浓度的测量在尼古丁摄入量方面提供了与血浆可替宁相同的信息。因此，唾液可替宁将是一种良好且侵入性较小的香烟烟雾暴露标志物，反映血浆可替宁浓度和动力学。
