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Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

ABSTRACT: Introduction: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. Methods: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. Results: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. Conclusions: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. Implications: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.

SUBMITTER: Teichert A

PROVIDER: S-EPMC5896440 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

Teichert Axel A Brossard Patrick P Felber Medlin Loyse L Sandalic Larissa L Franzon Mikael M Wynne Chris C Laugesen Murray M Lüdicke Frank F

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20180301 4

<h4>Introduction</h4>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.<h4>Methods</h4>This open-label, ascending nicotine levels study was conducted in 16 healthy smokers. Three different nicotine delivery levels, 50, 80, and 150 µg/puff, delivere ...[more]

PMID: 28482017

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Project description:IntroductionWe aimed to compare the pharmacokinetics of nicotine between the heat-not-burn Tobacco Heating System 2.1 (THS 2.1) and combustible cigarettes (CCs). We also examined whether the subjective urge to smoke was associated with the pharmacokinetics of nicotine.MethodsThis open-label, randomized, two-period, two-sequence crossover study conducted in 28 healthy smokers assessed the pharmacokinetics of nicotine after single and ad libitum use of the THS 2.1 or CCs. During the 7-day confinement period, blood samples were drawn for pharmacokinetic analysis. Subjective effects related to THS 2.1 or CC use were assessed using the Questionnaire of Smoking Urges (QSU-Brief).ResultsThe nicotine delivery rate was similar with the THS 2.1 and CCs after single and ad libitum use. The time to the maximum nicotine concentration was 8 minutes after single use of the THS 2.1 and CCs. The time to the peak concentration following ad libitum use was similar between the THS 2.1 and CCs. The maximum plasma nicotine concentration after single use of the THS 2.1 was 8.4 ng/mL, 70.3% of that obtained with CCs. A transient reduction from baseline in the urge to smoke of 40% was observed 15 minutes after the single use of both the THS 2.1 and CCs. The mean QSU-Brief total scores following single and ad libitum use were similar for the THS 2.1 and CCs.ConclusionsThese results suggest that the THS 2.1 effectively delivers nicotine and achieves similar pharmacokinetic profiles to CCs. The THS 2.1 also reduced the urge to smoke similarly to CCs.ImplicationsReducing exposure to toxicants and safer delivery of nicotine are among the strategies that may reduce the harm of smoking-related diseases. In the present study, we investigated the pharmacokinetics of nicotine and their effects on the urge to smoke using the THS 2.1. It was developed to replicate the ritual of smoking as closely as possible by providing nicotine in a way that mimics CC smoking, but limits pyrolysis and combustion by heating tobacco at a much lower temperature than CCs (heat-not-burn).

Project description:Background and aimsVaporized nicotine products (VNPs) can vary in important characteristics including size, shape, flavor and nicotine yield. We examined whether complex interactions among these characteristics could affect smokers' VNP perceptions and usage patterns.DesignA within-subject randomized cross-over trial.SettingRoswell Park Comprehensive Cancer Center, Buffalo, NY, USA.ParticipantsEighteen daily cigarette smokers.MeasurementsParticipants attended eight weekly visits during which they sampled six different VNPs (disposable, rechargeable, eGO, mod, e-Cigar and e-Pipe) with tobacco-flavored e-liquid. Prior to device use, participants completed product-ranking questionnaires. Participants completed controlled puffing sessions during each of the six trials, after which satisfaction questionnaires were completed and blood samples were taken.FindingsInitial perceptions showed that the smallest device (disposable) was ranked as safer compared with a larger device (e-Pipe) (P < 0.05). Participants rated the eGO and mod devices higher on satisfaction and enjoyment from use, taste, pleasantness, harshness ('throat hit') and speed of effect, but lower on perceived health risk and embarrassment from use (P < 0.05). All devices had a lower Cmax than the combustible cigarette (P < 0.05), but there were differences among devices (P < 0.05). The mod, e-Pipe and eGO provided the highest amount of perceived smoking urge relief, and this correlated strongly with Cmax across all devices (R2 = 0.8614, P = 0.007). The perceived speed of urge relief was not correlated with Tmax (R2 = 0.0035, P = 0.911) CONCLUSIONS: Daily cigarette smokers testing six types of vaporized nicotine products (VNPs) reported that they varied in taste, amount of withdrawal relief, harshness, embarrassment from use, perceived health risk and subjective and objective nicotine delivery. The eGO and mod models have properties that may make them most effective for cigarette substitution among smokers who intend to switch to a VNP.

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Dataset Information

Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

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Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

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