Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff.

Introduction: The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation.

Nicotine delivery and subjective effects of Swedish portion snus compared with 4 mg nicotine polacrilex chewing gum.

Introduction: Snus availability has been claimed to have contributed to the low rates of smoking among Swedish men and made possible the transfer to a less harmful form of nicotine dependence.

Methods: Fourteen cigarette smokers were randomly assigned to 2 types of 1 g Swedish portion snus and 4 mg nicotine polacrilex (NP) chewing gum in open-label, single-dose crossover study. Nicotine delivery and pharmacokinetics were estimated, and self-reports of subjective effects were obtained using Visual Analogue Scales (VASs).

Steady-state nicotine plasma levels following use of four different types of Swedish snus compared with 2-mg Nicorette chewing gum: a crossover study.

The present study evaluated nicotine plasma levels achieved following 1 day's regular use of four commonly used brands of Swedish portion snus and 2-mg Nicorette chewing gum. The study also estimated the amount of sodium chloride extracted from each snus sachet to identify potential risks for exacerbation of heart failure and hypertension with the use of Swedish snus. Extracted dose of nicotine, area under the venous plasma concentration-time curve (AUC), maximum plasma nicotine concentration (Cmax) of the last (12th) dosing interval, and the Cmax and AUC ratios versus Nicorette were calculated.

The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments.

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes, respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery.

Pharmacokinetic investigation of a nicotine sublingual tablet.

Objective: To evaluate the pharmacokinetics of a new 2-mg nicotine sublingual tablet under varying conditions of use.

Methods: The pharmacokinetics of the 2-mg nicotine sublingual tablet were investigated in four separate studies involving healthy adult volunteer smokers: (1) a multiple-dose comparison with 2-mg nicotine chewing gum (n=24; 13 males, 11 females), (2) a dose-proportionality study comparing single doses of 2, 4 and 6 mg (n=21, 10 males, 11 females), (3) an evaluation of the effect of incorrect tablet use, i.e.

Pharmacokinetics of nicotine in healthy elderly people.

Background: Mortality hazards of smoking extend well into later life; this suggests that smoking cessation will continue to improve life expectancy in older people. The pharmacology and pharmacokinetics of nicotine have not been studied in elderly subjects. Drug disposition and pharmacodynamic responsiveness to nicotine may change with age, and conclusions founded on data from studies of younger populations may not apply to elderly populations.

Reduction of tobacco withdrawal symptoms with a sublingual nicotine tablet: a placebo controlled study.

Many smokers are unable to use gum as a cessation aid due to fillings, bridgework and dyspepsia or they reject it for esthetic reasons. The nicotine sublingual tablet is a new alternative to the nicotine polacrilex chewing gum that does not necessitate chewing. Twenty subjects used 2-mg sublingual nicotine tablets and placebo in a double-blind randomized crossover study of 2-day smoke-free periods.

Pharmacokinetics of nicotine in kidney failure.

Background: Smoking is an important risk factor for cardiovascular and cerebrovascular complications in patients with chronic kidney failure. Very high plasma nicotine concentrations have been reported in patients with severe kidney failure, indicating that the disposition of nicotine in these patients may be different. The purpose of this study was to assess the pharmacokinetics of intravenously administered nicotine in healthy subjects and in patients with kidney failure.

Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function.

The role of platelets in cardiovascular disease associated with smoking is becoming more established, but the effects of nicotine on platelets are unclear. Nicotine therapy is used for smoking cessation in both health and disease. Consequently, the effects of nicotine on platelets are of particular significance in disorders such as renal disease, which is associated with defective platelet function, increased cardiovascular morbidity, and altered nicotine metabolism.

Site of nicotine absorption from a vapour inhaler--comparison with cigarette smoking.

Objective: The aim of the study was to assess the site of nicotine absorption during and after use of a nicotine-vapour inhaler compared with that after cigarette smoking.

Methods: Using a catheterisation technique, the nicotine plasma concentration-time profiles in arterial and jugular venous blood after using a nicotine inhaler were compared with those achieved after cigarette smoking a in seven healthy habitual smokers.

Results: After use of the inhaler, arterial nicotine concentrations rose slowly to a maximum level of 5.

Electroencephalographic effects of intravenous nicotine--a dose-response study.

Rationale: It has often been demonstrated that both tobacco abstinence and nicotine have effects on the EEG power spectrum and components of the event-related potentials. In contrast, few attempts have been made to establish the dose-response relationship between nicotine and EEG parameters.

Objectives: The aim of this study was to investigate the dose-response relationship for EEG and auditory oddball P300 parameters over a wide range of intravenously infused nicotine doses.

Aiding reduction of smoking with nicotine replacement medications: hope for the recalcitrant smoker?

Objective: To assess the effect of the various nicotine replacement therapies (NRT) on smoking reduction.

Design: During an initial sampling week, the subjects familiarised themselves with nicotine gum, patch, nasal spray, vaporiser (vapour inhaler) and sublingual tablet. A crossover design was used during the next four study weeks; during two of these weeks the subjects could select one nicotine replacement product of their choice to use, whereas during the other two they were randomly assigned a product to use.

Temperature dependency of the release and bioavailability of nicotine from a nicotine vapour inhaler; in vitro/in vivo correlation.

Objective: To investigate the temperature dependency of the dose released and the plasma levels of nicotine from a vapour inhaler.

Methods: In an open, randomised, three-way cross-over pharmacokinetic study 18 healthy subjects inhaled nicotine for 20 min (80 inhalations) every hour for 10 h (11 administrations) at three different environmental temperatures: 20 degrees, 30 degrees and 40 degrees C. In the in vitro experiment, 5, 10, 15 and 20 l air were forced through the inhaler.

Exposure to high ambient temperature increases absorption and plasma concentrations of transdermal nicotine.

Absorption and plasma concentrations of transdermally delivered drugs may be increased during heat exposure. We studied the effects of short-term heat exposure in a sauna bath on the pharmacokinetics of transdermal nicotine, 25 mg/16 hr, in 12 healthy smokers in an open, randomized crossover study that consisted of a control session and a sauna bathing session. In the sauna session the subjects stayed seated in a sauna bath (mean temperature 82 degrees C (180 degrees F); mean relative humidity 28%) for three 10-minute periods separated by two 5-minute breaks.

Clinical pharmacokinetics of nasal nicotine delivery. A review and comparison to other nicotine systems.

Rapid drug delivery (arterial "boli') and high drug concentrations occur with nicotine inhaled in smoke. These are believed to be key elements in producing addiction to cigarettes. Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduced as treatments for smoking cessation.

Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler.

In an open, randomized, three-way crossover study, 14 healthy smokers used one type of nicotine vapor inhaler intensely for 20 minutes every hour for 11 hours (12 administrations). Two different inhalation techniques were applied, shallow frequent sucking (buccal mode) and deep inhalations (pulmonary mode). The determination of nicotine was performed by capillary gas chromatography after single-step liquid-liquid extraction of the plasma sample.

Transdermally administered nicotine accumulates in gastric juice.

Methods: Transdermal nicotine patches (Nicorette 15 mg.16 h-1) were administered to 7 healthy volunteers. Nicotine concentrations in gastric juice were monitored for 8 h via a naso-gastric tube and so was nicotine in saliva and plasma.

Regional deposition of inhaled 11C-nicotine vapor in the human airway as visualized by positron emission tomography.

The deposition of 11C-nicotine in the respiratory tract from a nicotine vapor inhaler was studied by means of positron emission tomography (PET) in an intrasubject comparison of six healthy smokers using two modes of inhalation: one with shallow, frequent inhalations ("buccal mode") and one with deep inhalations ("pulmonary mode"). An average of 15% of the radioactivity was released from the vapor inhaler after 5 minutes of inhalation. Approximately 45% of the dose released was found in the oral cavity.

Effect of nicotine vapour inhalation on the relief of tobacco withdrawal symptoms.

Fifteen subjects participated in a randomised, placebo-controlled cross-over study to assess the effect of a nicotine vapour inhaler on craving and other withdrawal symptoms during a two-day smoking-free period. Craving and withdrawal symptoms were rated nine times over the two-day period on 10 cm visual analogue scales. Plasma nicotine concentrations in the afternoon of each study day were determined.

Relative bioavailability of nicotine from a nasal spray in infectious rhinitis and after use of a topical decongestant.

The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state.

Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms.

Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation. This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone. Twenty-eight smokers served as their own controls in each of four conditions: active gum + active patch (double active), active gum + placebo patch (gum only active), placebo gum + active patch (patch active) and placebo gum + placebo patch (double placebo).

No effect of roxithromycin on pharmacokinetic or pharmacodynamic properties of warfarin and its enantiomers.

The macrolide antibiotics are metabolized by cytochrome P-450 enzymes in the liver and interactions with similarly metabolized compounds have been described. Simultaneous treatment with erythromycin and warfarin is known to decrease warfarin clearance and prolong prothrombin time. Roxithromycin (RU 28965), a new erythromycin derivative with improved pharmacokinetic properties, might then, because of structure similarity, be expected to interact with warfarin.

Pharmacokinetics of enprofylline in healthy elderly subjects.

The pharmacokinetics of enprofylline, a new potent antiasthmatic, has been studied in 20 healthy, elderly subjects, aged 65 to 81 years, and in 7 young adult controls, aged 23 to 37 years. The dose of 1 mg/kg body weight was given as an i.v.

Additive bronchodilator effects of terbutaline and enprofylline in asthma.

Enprofylline is a novel xanthine derivative with negligible adenosine antagonizing ability. It is eliminated almost exclusively by renal clearance with a half-life of about 2 h. Three i.