Today various tobacco and nicotine products are available, many of them can be regarded as potentially risk-reduced products when compared to the most frequently used product, combustible cigarettes (CCs). A commonality of these products is that they deliver nicotine, although in quite different amounts and uptake routes, the most common of which are inhalation through the lung and absorption through the oral mucosa. Product-specific nicotine delivery as well as the subject-related use patterns are important factors which determine the pharmacokinetics and achieved internal dose levels of the alkaloid. The latter two parameters are highly relevant for the long-term product loyalty and, consequently, for the implicated health risks, since the risk-reduced products will replace CCs in the long-term only when users will experience a similar level of satisfaction. We measured nicotine and its major metabolites in plasma, saliva and urine samples collected in a controlled clinical study with habitual users (10 per group) of CCs, electronic cigarettes (ECs), heated tobacco products (HTP), oral tobacco (OT), and nicotine replacement therapy (NRT). Non-users (NU) of any tobacco/nicotine products served as (negative) control group. Moderate to strong correlations were observed between the daily consumption and the urinary nicotine equivalents (comprising nicotine and its 10 major metabolites, Nic + 10) or plasma and saliva cotinine concentrations. The average daily nicotine dose as measured by the urinary excretion of Nic + 10 (reflecting approximately 95 % of the absorbed nicotine) amounted to 17 and 22 mg/24 h for smokers (CC) and OT users, respectively, while it was in the range of 6-12 mg/24 h for users of ECs, HTP and NRT products, with high inter-individual variations in each user group. The individual daily nicotine intake, which was calculated by applying product-specific models, showed none to good agreement with the corresponding internal nicotine dose measured by Nic + 10 excretion. Possible reasons for the observed deviations between calculated and objectively measured nicotine doses are discussed.
Keywords: 3-OH-Cot, trans-3′-hydroxycotinine; 3-OH-Cot-gluc, trans-3′-hydroxycotinine-N,O-glucuronide; B, blood; CC, combustible cigarettes; CI, 95%-confidence interval; CNO, cotinine-N-1-oxide; Combustible cigarettes; Cot, cotinine; Cot-gluc, cotinine-N-glucuronide; EC, electronic cigarettes; Electronic cigarettes; HTP, heated tobacco product; Heated tobacco products; Hypybut, 4-OH-4-(3-pyridyl)-butanoic acid; IQR, inter-quartile range (25th–75th percentile); LC-MS/MS, liquid chromatography with tandem mass spectrometry; NCot, norcotinine; NNO, nicotine-N-1′-oxide; NNic, nornicotine; NRT, nicotine replacement therapy; NU, non-user of any tobacco/nicotine product; Nequ, nicotine equivalents; Nic+10, nicotine and its 10 major metabolites Cot, 3-OH-Cot, Nic-gluc, Cot-gluc, 3-OH-Cot-gluc, NNic, NCot, NNO, CNO, Hypybut; Nic, nicotine; Nic-gluc, nicotine-N’-glucuronide; Nicotine; Nicotine gum; OT, oral tobacco; P, plasma; S, saliva; SD, standard deviation of the mean; SEM, standard error of the mean; Snus; U, urine.
© 2022 The Authors.