Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.
Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.
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DOI：
10.1093/ntr/ntx093
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发表时间：
2018-03-06
期刊：
影响因子：
--
通讯作者：
Lüdicke F
中科院分区：
文献类型：
--
作者：
Teichert A;Brossard P;Felber Medlin L;Sandalic L;Franzon M;Wynne C;Laugesen M;Lüdicke F
新型尼古丁输送系统代表了烟草危害减少战略的一个不断发展的部分。评价了通过P3 L（一种肺部尼古丁给药系统）给药的尼古丁药代动力学（PK）特征及其对尼古丁吸入器相关的吸烟欲望和烟瘾缓解的影响。这项开放标签、尼古丁水平上升的研究在16名健康吸烟者中进行。在使用尼古丁吸入器后的不同日期，连续评价了通过P3 L系统递送的三种不同尼古丁递送水平（50、80和150 µg/喷）。评估静脉尼古丁PK、主观效应和耐受性。通过暴露量比较的混合效应模型生成的最大血浆尼古丁浓度（Cmax）的几何最小二乘均值分别为9.7、11.2和9.8 ng/mL（50、80和150 µg/揿P3 L变体），而使用尼古丁吸入器后为6.1 ng/mL。所有P3 L从产品使用开始至Cmax的中位时间为7.0分钟，而Nicorette吸入器为30.0分钟。根据视觉模拟量表渴求评分评估，渴求减少略快于尼古丁吸入器。两种产品的平均吸烟冲动问卷-简要总分没有差异。P3 L耐受性良好。在检测的所有三种尼古丁水平下，与Nicorette吸入器相比，吸入P3 L递送的乳酸尼古丁气雾剂可提供更高和更快的血浆尼古丁浓度。与Nicorette吸入器的oromuclide吸收相比，血浆尼古丁浓度-时间曲线支持P3 L的肺部吸收途径。尼古丁和乳酸与P3 L装置的组合显示出优于现有尼古丁递送系统的潜力，其递送尼古丁的动力学接近于传统香烟的已发表数据，并且不含当前电子尼古丁递送系统中使用的外源性载体物质。总之，本研究中获得的PK特征、主观效应和安全性特征表明，P3 L是一种创新的尼古丁给药产品，可被成年吸烟者接受作为香烟的替代品。
Novel nicotine delivery systems represent an evolving part of the tobacco harm reduction strategy. The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette inhalator were evaluated. This open-label, ascending nicotine levels study was conducted in 16 healthy smokers. Three different nicotine delivery levels, 50, 80, and 150 µg/puff, delivered by the P3L system were evaluated consecutively on different days after the use of the Nicorette inhalator. Venous nicotine PK, subjective effects, and tolerability were assessed. Geometric least-squares means for maximum plasma nicotine concentration (Cmax), generated by the mixed-effect model for exposure comparison, were 9.7, 11.2, and 9.8 ng/mL for the 50, 80, and 150 µg/puff P3L variants, respectively, compared to 6.1 ng/mL after Nicorette inhalator use. Median time from product use start to Cmax was 7.0 minutes for all P3L, compared to 30.0 minutes for the Nicorette inhalator. Craving reduction was slightly faster than with the Nicorette inhalator as assessed with the visual analog scale craving score. The mean Questionnaire of Smoking Urges -brief total scores did not differ for both products. P3L was well tolerated. At all three nicotine levels tested, the inhalation of the nicotine lactate aerosol delivered with the P3L provided plasma nicotine concentrations higher and faster compared to the Nicorette inhalator. The plasma nicotine concentration–time profile supports a pulmonary route of absorption for P3L compared to the oromucosal absorption of the Nicorette inhalator. The combination of nicotine and lactic acid with the P3L device shows potential over existing nicotine delivery systems by delivering nicotine with kinetics close to published data on conventional cigarettes and without exogenous carrier substances as used in current electronic nicotine delivery systems. Altogether, the PK profile, subjective effects, and safety profile obtained in this study suggest P3L is an innovative nicotine delivery product that will be acceptable to adult smokers as an alternative to cigarettes.
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影响因子：
6
作者：
Helen, Gideon St.;Havel, Christopher;Benowitz, Neal L.
通讯作者：
Benowitz, Neal L.
影响因子：
4.7
作者：
Kraiczi, Holger;Hansson, Anna;Perfekt, Roland
通讯作者：
Perfekt, Roland
影响因子：
4.6
作者：
Farsalinos, Konstantinos E.;Spyrou, Alketa;Voudris, Vassilis
通讯作者：
Voudris, Vassilis
影响因子：
4.7
作者：
Moyses, Chris;Hearn, Alex;Redfern, Andrew
通讯作者：
Redfern, Andrew
DOI：
10.1056/nejmsa1502403
发表时间：
2015-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Donny EC;Denlinger RL;Tidey JW;Koopmeiners JS;Benowitz NL;Vandrey RG;al'Absi M;Carmella SG;Cinciripini PM;Dermody SS;Drobes DJ;Hecht SS;Jensen J;Lane T;Le CT;McClernon FJ;Montoya ID;Murphy SE;Robinson JD;Stitzer ML;Strasser AA;Tindle H;Hatsukami DK
通讯作者：
Hatsukami DK