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. Comparison is made to Swedish General snus and American Longhorn moist snuff and from literature 4 mg Nicorette gum and mean of 13 brands of e-cigarettes. AIMS AND METHODS: A single-dose randomized crossover design was used. In vivo extraction and PK parameters were determined. RESULTS: Part 1. The AUCinf of ZYN 3 mg was 27% smaller than that of 8 mg General and the AUCinf of ZYN 6 mg was 34% larger than that of 8 mg General. Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg General (32%). RESULTS: Part 2. Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN 8 mg and Longhorn Natural 18 mg moist snuff. The extracted amount of nicotine from ZYN 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg), but smaller than the extracted amount of nicotine from General 2 × 8 mg snus pouches (5.0 mg). The extracted fraction of nicotine for ZYN 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2 × 8 mg snus pouches (33%). CONCLUSIONS: The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects.

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). RESULTS: Extracted dose from the NP gum averaged 2.56 mg compared with 2.12 and 2.18 mg, respectively, for Swedish portion snus. This resulted in a slightly larger area under the curve (AUC) for the NP chewing gum. The rise of the nicotine plasma concentration was faster for Swedish snus. Median T(max) was shorter, 30 min for snus compared with 45 min for the NP gum. The lower C(max) of NP gum compared with the snus products in spite of larger AUC may be explained by slower absorption from the chewing gum. The faster absorption of nicotine from Swedish portion snus was mirrored in a higher VAS score for "head rush." Craving/urges to smoke decreased similarly for all treatments. Salivation and throat burn were rated higher for the 4 mg NP gum compared with both types of snus. CONCLUSIONS: Swedish snus produced higher maximum blood nicotine concentration in shorter time and with a quicker onset of "head rush" compared with 4 mg NP chewing gum in spite of a smaller extracted dose. The quicker onset of "head rush" and supposedly higher satisfaction from snus may partly explain the widespread use of snus for stopping smoking in Sweden.

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. Relative bioavailable dose was calculated using AUC of 2-mg Nicorette gum as the reference. The mean extracted nicotine doses were 2.74+/-0.80, 1.55+/-0.68, 2.00+/-0.56, and 1.08+/-0.94 mg/sachet for General, Catch Licorice, Catch Mini, and Catch Dry Mini snus, respectively. The approximate bioavailable dose of nicotine from snus was 40%-60% of the extracted dose. The steady-state nicotine plasma concentration-time curve for the weakest brand, Catch Dry Mini portion snus, did not differ significantly from that of the 2-mg Nicorette gum. The AUC and Cmax for Catch Licorice 1 g and Catch Mini 0.5 g portion snus were twice those for the 2-mg Nicorette gum; for the strongest brand, General, these values were 2(1/2) times those for Nicorette gum. The differences in AUC and Cmax versus the 2-mg Nicorette gum were statistically significant (p=.020). Nicotine plasma levels with General portion snus were sustained at higher levels than current nicotine replacement therapy products, peaking at 29.0+/-8.5 ng/ml, and more closely mimicking cigarette smokers' nicotine plasma levels. The risks of aggravation of heart failure and hypertension with respect to increased salt load from the use of snus appeared to be negligible.