Assessing Nicotine Pharmacokinetics of New-Generation Tobacco Products and Conventional Cigarettes: A Systematic Review and Meta-analysis

Abstract Introduction New-generation tobacco products (NGPs) hold promises as modified-risk alternatives to conventional cigarettes (CCs), given their comparable characteristics. This study investigated the nicotine pharmacokinetics (PK) of NGPs, encompassing closed pod systems, refillable e-cigarettes (ECs), and heated tobacco products (HTPs), in comparison to CCs through systematic review and meta-analysis. Aims and Methods A comprehensive search was conducted on PubMed, Embase, and Web of Science for articles published between January 2013 and July 2023. Maximum nicotine concentration (Cmax), time to peak concentration (Tmax), and total nicotine exposure (area under the concentration-time curve, AUC) were extracted to evaluate nicotine delivery PK. Random effects meta-analyses were performed to determine pooled standardized mean differences, facilitating a comparison of PK profiles between NGPs and CCs. Subgroup analyses exploring flavors and nicotine concentrations across NGPs, and CCs were also conducted. Results The meta-analysis incorporated 30 articles with 2728 participants. Cmax and AUC were significantly lower for NGPs, while Tmax demonstrated statistical similarity compared to CCs. Among three NGPs, Cmax, and AUC were lower for closed pod systems and refillable ECs. In HTPs, Cmax was statistically similar while AUC was lower compared to CCs. Tmax was statistically similar in closed pod systems and HTPs compared to that of CCs. No significant difference was observed in the comparisons of PK between each type of NGPs versus CCs. Conclusions NGPs delivered less nicotine than CCs but reached Cmax over a similar timeframe, indicating that NGPs may serve as modified-risk alternatives with lower nicotine delivery to CCs for craving relief and smoking cessation. Implications This study suggested that NGPs, such as the closed pod systems, the refillable ECs, and the HTPs, delivered either lower or comparable nicotine levels and achieved peak nicotine concentration at a similar rate as CCs. Our findings carry implications that NGPs can serve as modified-risk nicotine alternatives to CCs in helping smokers manage cravings and potentially quit smoking, thereby highlighting their value in the field of tobacco harm reduction.