Chin B. Eap

Background Popular “pod-style” e-cigarettes commonly use nicotine salt-based e-liquids that cause less irritation when inhaled and can deliver higher nicotine concentrations than free-base nicotine. We aimed to investigate the pharmacokinetic and pharmacodynamic effects of different nicotine formulations (salt vs. free-base) and concentrations that might influence systemic nicotine absorption and appeal of e-cigarettes. Methods In this randomized, double-blind, within-subject crossover study, 20 non nicotine-naïve participants were switched among three e-liquids (free-base nicotine 20mg/mL, nicotine salt 20mg/mL, nicotine salt 40mg/mL) using a refillable pod system and a standardized vaping protocol (one puff every 30 seconds, 10 puffs total). Serum nicotine concentrations and vital signs were assessed over 180 minutes; direct effects, craving, satisfaction, withdrawal, and respiratory symptoms were measured using questionnaires. CYP2A6 genotypes and the nicotine metabolite ratio were also assessed. Results Eleven (55%) participants were male and the median age was 23.5 years (range 18-67). All three formulations differed significantly in peak serum nicotine concentration (baseline adjusted Cmax, median (range): 12.0ng/mL (1.6-27.3), 5.4ng/mL (1.9-18.7) and 3.0ng/mL (1.3-8.8) for nicotine salt 40mg/mL, nicotine salt 20mg/mL and free-base 20mg/mL, respectively). All groups reached Cmax 2.0-2.5min (median) after their last puff. Differences in subjective effects were not statistically significant. No serious adverse events were observed. Conclusion Free-base 20mg/mL formulations achieved lower blood nicotine concentrations than nicotine salt 20mg/mL, while 40mg/mL nicotine salt yielded concentrations similar to cigarette smoking. The findings can inform regulatory policy regarding e-liquids and their potential use in smoking cessation. Implications Nicotine salt formulations inhaled by an e-cigarette led to higher nicotine delivery compared to nicotine free-base formulations with the same nicotine concentration. These findings should be considered in future regulatory discussions. The 40mg/mL nicotine salt formulation showed similar nicotine delivery as combustible cigarettes, albeit at concentrations over the maximum limit for e-liquids allowed in the European Union. Nicotine delivery resembling combustible cigarettes might be beneficial for smokers willing to quit to adequately alleviate withdrawal symptoms. However, increased nicotine delivery can also pose a public health risk, raising concerns about abuse liability, especially among youth and non-smokers.

Metabolic abnormalities have been associated with olanzapine treatment. We assessed if olanzapine has dose‐dependent effects on metabolic parameters with changes for weight, blood pressure, lipid and glucose profiles being modelled using linear mixed‐effects models. The risk of metabolic abnormalities including early weight gain (EWG) (≥5% during first month) was assessed using mixed‐effects logistic regression models. In 392 olanzapine‐treated patients (median age 38.0 years, interquartile range [IQR] = 26.0–53.3, median dose 10.0 mg/day, IQR = 5.0–10.0 for a median follow‐up duration of 40.0 days, IQR = 20.7–112.2), weight gain was not associated with olanzapine dose ( p = 0.61) although it was larger for doses versus ≤10 mg/day (2.54 ± 5.55 vs. 1.61 ± 4.51% respectively, p = 0.01). Treatment duration and co‐prescription of >2 antipsychotics, antidepressants, benzodiazepines and/or antihypertensive agents were associated with larger weight gain ( p < 0.05). Lower doses were associated with increase in total and HDL cholesterol and systolic and diastolic blood pressure ( p < 0.05), whereas higher doses were associated with glucose increases ( p = 0.01). Patients receiving >10 mg/day were at higher EWG risk (odds risk: 2.15, 1.57–2.97). EWG might be prominent in high‐dose olanzapine‐treated patients with treatment duration and co‐prescription of other medications being weight gain moderators. The lack of major dose‐dependent patterns for weight gain emphasizes that olanzapine‐treated patients are at weight gain risk regardless of the dose.