在一项随机交叉研究中评估全球加热烟草产品的滥用可能性和尼古丁药代动力学。

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Milly N Kanobe, Patrudu Makena, Kristen Prevette, Sarah A Baxter
{"title":"在一项随机交叉研究中评估全球加热烟草产品的滥用可能性和尼古丁药代动力学。","authors":"Milly N Kanobe, Patrudu Makena, Kristen Prevette, Sarah A Baxter","doi":"10.1007/s13318-024-00921-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Nicotine uptake, as reflected in the area under the curve (AUC) at 15 and 240 min after product use (AUC<sub>0-15</sub> and AUC<sub>0-240</sub>, respectively) and maximum nicotine concentration (C<sub>max</sub>) were significantly lower for all glo HTPs compared to UB cigarettes, regardless of the glo device mode. AUC<sub>0-15</sub> 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<sub>0-240</sub> 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<sub>max</sub> for glo HTPs ranged from 5.46 to 9.00 ng/mL, whereas UB cigarettes had C<sub>max</sub> values of 16.29 to 16.76 ng/mL. The time to reach maximum nicotine concentration (T<sub>max</sub>) 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<sub>max</sub> of 45 min and C<sub>max</sub> of 4.60 ng/mL. AUC<sub>0-15</sub> and AUC<sub>0-240</sub> 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, smoking urge reduction, product effects, and intent to use again, but were comparable to nicotine gum.</p><p><strong>Conclusion: </strong>glo HTPs demonstrated lower AL than combustible cigarettes while delivering sufficient nicotine to support product adoption among current smokers. This positions glo HTPs as a potential tool in tobacco harm reduction, offering a less harmful alternative to traditional cigarettes.</p><p><strong>Trial registry: </strong>Clinical trial ID NCT05114863.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"733-750"},"PeriodicalIF":1.9000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549183/pdf/","citationCount":"0","resultStr":"{\"title\":\"Assessment of Abuse Liability and Nicotine Pharmacokinetics of glo Heated Tobacco Products in a Randomized, Crossover Study.\",\"authors\":\"Milly N Kanobe, Patrudu Makena, Kristen Prevette, Sarah A Baxter\",\"doi\":\"10.1007/s13318-024-00921-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Nicotine uptake, as reflected in the area under the curve (AUC) at 15 and 240 min after product use (AUC<sub>0-15</sub> and AUC<sub>0-240</sub>, respectively) and maximum nicotine concentration (C<sub>max</sub>) were significantly lower for all glo HTPs compared to UB cigarettes, regardless of the glo device mode. AUC<sub>0-15</sub> 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<sub>0-240</sub> 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<sub>max</sub> for glo HTPs ranged from 5.46 to 9.00 ng/mL, whereas UB cigarettes had C<sub>max</sub> values of 16.29 to 16.76 ng/mL. The time to reach maximum nicotine concentration (T<sub>max</sub>) 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<sub>max</sub> of 45 min and C<sub>max</sub> of 4.60 ng/mL. AUC<sub>0-15</sub> and AUC<sub>0-240</sub> 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, smoking urge reduction, product effects, and intent to use again, but were comparable to nicotine gum.</p><p><strong>Conclusion: </strong>glo HTPs demonstrated lower AL than combustible cigarettes while delivering sufficient nicotine to support product adoption among current smokers. This positions glo HTPs as a potential tool in tobacco harm reduction, offering a less harmful alternative to traditional cigarettes.</p><p><strong>Trial registry: </strong>Clinical trial ID NCT05114863.</p>\",\"PeriodicalId\":11939,\"journal\":{\"name\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"volume\":\" \",\"pages\":\"733-750\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549183/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13318-024-00921-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Drug Metabolism and Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13318-024-00921-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

背景和目的:加热烟草制品(HTPs)是一类不可燃的吸入式烟草制品,由于减少了卷烟烟雾中有毒物质的暴露,因此有可能降低与吸烟相关的危害。在产品使用过程中进行的主观和尼古丁药代动力学测量为烟草和尼古丁产品的滥用责任(AL)评估提供了一个框架,也为新烟草产品的采用潜力提供了信息,这些都是美国食品药品管理局对上市前烟草产品授权的重要方面。本研究旨在评估以标准模式或提升模式运行的全球热吸入器与高AL和低AL参照物(分别为受试者的常用品牌香烟和尼古丁口香糖)相比的AL值:方法:在一项临床研究中,采用开放标签、随机交叉研究设计,对75名健康的非薄荷或薄荷醇成年吸烟者进行了尼古丁摄取和药效学测量(包括主观和生理测量)。在全球 HTPs(标准或增压模式)与普通品牌(UB)香烟和尼古丁口香糖之间进行了比较,以评估尼古丁摄入量和主观效应指标:使用产品后15分钟和240分钟的尼古丁摄入量曲线下面积(AUC)(分别为AUC0-15和AUC0-240)和最大尼古丁浓度(Cmax)均显著低于普通卷烟,而与glo HTPs相比,无论采用哪种glo装置模式。全球 HTPs 的 AUC0-15 值介于 41.26 至 75.71 纳克 × 分钟/毫升之间,而 UB 香烟的 AUC0-15 值介于 158.04 至 165.53 纳克 × 分钟/毫升之间。同样,glo HTPs 的 AUC0-240 值为 379 至 596 纳克 × 分钟/毫升,而 UB 香烟的 AUC0-240 值为 1123.73 和 1283.37 纳克 × 分钟/毫升。glo HTPs 的 Cmax 值为 5.46 至 9.00 纳克/毫升,而 UB 香烟的 Cmax 值为 16.29 至 16.76 纳克/毫升。达到最大尼古丁浓度(Tmax)的时间(4-5 分钟)明显短于达到最大尼古丁浓度(6-7 分钟)的 UB 香烟,只有一种标准模式的 glo HTP 除外。尼古丁口香糖的尼古丁吸收曲线较慢,Tmax 为 45 分钟,Cmax 为 4.60 纳克/毫升。尼古丁口香糖的 AUC0-15 和 AUC0-240 值分别为 6.18 和 5.22 纳克 × 分钟/毫升,非薄荷组和薄荷组的 AUC0-15 和 AUC0-240 值分别为 647.80 和 687.68 纳克 × 分钟/毫升。主观测量结果显示,glo HTPs在产品喜好、吸烟冲动减少、产品效果和再次使用意愿方面的评分明显低于UB香烟,但与尼古丁口香糖相当。这将全球 HTPs 定位为减少烟草危害的潜在工具,为传统香烟提供了一种危害较小的替代品:临床试验 ID NCT05114863。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Assessment of Abuse Liability and Nicotine Pharmacokinetics of glo Heated Tobacco Products in a Randomized, Crossover Study.

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 (AUC0-15 and AUC0-240, respectively) and maximum nicotine concentration (Cmax) were significantly lower for all glo HTPs compared to UB cigarettes, regardless of the glo device mode. AUC0-15 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, AUC0-240 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 Cmax for glo HTPs ranged from 5.46 to 9.00 ng/mL, whereas UB cigarettes had Cmax values of 16.29 to 16.76 ng/mL. The time to reach maximum nicotine concentration (Tmax) 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 Tmax of 45 min and Cmax of 4.60 ng/mL. AUC0-15 and AUC0-240 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, smoking urge reduction, product effects, and intent to use again, but were comparable to nicotine gum.

Conclusion: glo HTPs demonstrated lower AL than combustible cigarettes while delivering sufficient nicotine to support product adoption among current smokers. This positions glo HTPs as a potential tool in tobacco harm reduction, offering a less harmful alternative to traditional cigarettes.

Trial registry: Clinical trial ID NCT05114863.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信