Assessment of Abuse Liability and Nicotine Pharmacokinetics of glo Heated Tobacco Products in a Randomized, Crossover Study

• Published in: European journal of drug metabolism and pharmacokinetics 2024-11, Vol.49 (6), p.733-750
• Main Authors: Kanobe, Milly N., Makena, Patrudu, Prevette, Kristen, Baxter, Sarah A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Cross-Over Studies; Female; Hot Temperature; Human Physiology; Humans; Male; Medical Biochemistry; Middle Aged; NCT; NCT05114863; Nicotine - pharmacokinetics; Nicotine Chewing Gum; Original; Original Research Article; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy; Tobacco Products; Tobacco Use Disorder; Young Adult
• ISSN: 0378-7966; 2107-0180; 2107-0180
• DOI: 10.1007/s13318-024-00921-4

Background and Objective Heated tobacco products (HTPs) are a class of non-combustible, inhaled tobacco products with the potential to reduce the harm associated with cigarette smoking due to reduced cigarette smoke toxicant exposure. Subjective and nicotine pharmacokinetics measures taken over the course of product use provide a framework for abuse liability (AL) assessment of tobacco and nicotine products as well as information on adoption potential for a new tobacco product, which are important aspects for premarket tobacco product authorization by the US Food and Drug Administration. This study aimed to assess the AL of glo HTPs, operated in either Standard or Boost Modes, compared with high- and low-AL comparators (subjects’ usual brand cigarettes and nicotine gum, respectively). Methods Nicotine uptake and pharmacodynamics measures (including subjective and physiological measures) were assessed in a clinical study of 75 healthy adult non-menthol or menthol smokers using an open-label, randomized crossover study design. Comparisons were made between glo HTPs (Standard or Boost Modes) and each of usual brand (UB) cigarettes and nicotine gum to evaluate nicotine exposure and subjective effects measures. Results Nicotine uptake, as reflected in the area under the curve (AUC) at 15 and 240 min after product use (AUC 0-15 and AUC 0-240 , respectively) and maximum nicotine concentration (C max ) were significantly lower for all glo HTPs compared to UB cigarettes, regardless of the glo device mode. AUC 0-15 values for glo HTPs ranged from 41.26 to 75.71 ng × min/mL, versus 158.04 to 165.53 ng × min/mL for UB cigarettes. Similarly, AUC 0-240 values for glo HTPs ranged from 379 to 596 ng × min/mL, compared to 1123.73 and 1283.37 ng × min/mL for UB cigarettes. The C max for glo HTPs ranged from 5.46 to 9.00 ng/mL, whereas UB cigarettes had C max values of 16.29 to 16.76 ng/mL. The time to reach maximum nicotine concentration (T max ) was significantly shorter for glo HTPs (4–5 min) compared to UB cigarettes (6–7 min), except for one variant of glo HTP in Standard Mode. Nicotine gum exhibited a slower nicotine absorption profile, with a T max of 45 min and C max of 4.60 ng/mL. AUC 0-15 and AUC 0-240 values for nicotine gum were 6.18 and 5.22 ng × min/mL, and 647.80 and 687.68 ng × min/mL for non-menthol and menthol groups, respectively. Subjective measures indicated that glo HTPs were rated significantly lower than UB cigarettes in terms of product liking, smoki