Philip Morris Products S.A., Research & Development, Neuchâtel, Switzerland.
Christchurch Clinical Studies Trust Ltd., Christchurch, New Zealand.
Nicotine Tob Res. 2018 Mar 6;20(4):458-465. doi: 10.1093/ntr/ntx093.
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.
新型尼古丁输送系统是烟草减害策略的一个不断发展的组成部分。本研究评估了一种肺部尼古丁输送系统 P3L 输送的尼古丁的药代动力学（PK）特征及其与尼科莱特吸入器相比对吸烟冲动和缓解渴望的影响。
这是一项开放标签、递增尼古丁水平的研究，在 16 名健康吸烟者中进行。在使用尼科莱特吸入器后，连续在不同的日子评估 P3L 系统输送的 50、80 和 150μg/吸三种不同的尼古丁输送水平。评估了静脉内尼古丁 PK、主观效应和耐受性。
通过暴露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 50、80 和 150μg/吸 P3L 变体的 9.7、11.2 和 9.8ng/mL，而尼科莱特吸入器使用后的 Cmax 为 6.1ng/mL。所有 P3L 的从产品使用开始到 Cmax 的中位时间为 7.0 分钟，而尼科莱特吸入器为 30.0 分钟。使用视觉模拟量表渴望评分评估时，渴望缓解的速度略快于尼科莱特吸入器。两种产品的简短吸烟冲动问卷总评分没有差异。P3L 耐受性良好。
在测试的所有三个尼古丁水平下，与尼科莱特吸入器相比，用 P3L 输送的乳酸盐气溶胶吸入提供了更高和更快的血浆尼古丁浓度。与尼科莱特吸入器的口腔粘膜吸收相比，P3L 的血浆尼古丁浓度-时间曲线支持其肺部吸收途径。
与现有的尼古丁输送系统相比，P3L 装置将尼古丁与乳酸结合具有潜力，其动力学接近已发表的关于传统香烟的尼古丁数据，并且没有像当前电子尼古丁输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、主观效应和安全性概况表明，P3L 是一种创新的尼古丁输送产品，作为香烟的替代品，将被成年吸烟者接受。
