Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers

Gubner, Noah R.; Kozar-Konieczna, Aleksandra; Szołtysek-Bołdys, Izabela; Słodczyk-Mańkowska, Ewa; Goniewicz, Jerzy; Sobczak, Andrzej; Jacob, Peyton; Benowitz, Neal L.; Goniewicz, Maciej Ł.

doi:10.1016/j.drugalcdep.2016.04.006

Cited by 28 publications

(29 citation statements)

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“…To account for this difference, CYP2A6-k cat was estimated separately for the smoker subpopulation, leading to a lower k cat in comparison to the non-smoker subpopulation (see Table 1). [15,22,23]. Moreover, predicted bioavailabilities after oral (~ 35%) and pulmonary (~ 85%) administration of nicotine are in concordance with the literature (20-45% and 80-90%, respectively) [9,15,46].…”

Section: (B)supporting

confidence: 86%

“…Distribution and elimination processes including CYP enzymes and transporters were implemented according to the literature [ 15 , 21 – 23 ]. For the nicotine model, these are (1) metabolism of nicotine to its major metabolite cotinine through CYP2A6 and CYP2B6, (2) an unspecific hepatic clearance being responsible for the remaining hepatic metabolism of nicotine including metabolism via uridine 5ʹ-diphospho-glucuronosyltransferase 2B10 (UGT2B10) and flavin-containing monooxygenase 3 (FMO3), and (3) two transporters for the influx and efflux of nicotine across the blood–brain barrier (BBB).…”

Section: Methodsmentioning

confidence: 99%

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Comprehensive Parent–Metabolite PBPK/PD Modeling Insights into Nicotine Replacement Therapy Strategies

et al. 2020

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Background Nicotine, the pharmacologically active substance in both tobacco and many electronic cigarette (e-cigarette) liquids, is responsible for the addiction that sustains cigarette smoking. With 8 million deaths worldwide annually, smoking remains one of the major causes of disability and premature death. However, nicotine also plays an important role in smoking cessation strategies. Objectives The aim of this study was to develop a comprehensive, whole-body, physiologically based pharmacokinetic/ pharmacodynamic (PBPK/PD) model of nicotine and its major metabolite cotinine, covering various routes of nicotine administration, and to simulate nicotine brain tissue concentrations after the use of combustible cigarettes, e-cigarettes, nicotine gums, and nicotine patches. Methods A parent-metabolite, PBPK/PD model of nicotine for a non-smoking and a smoking population was developed using 91 plasma and brain tissue concentration-time profiles and 11 heart rate profiles. Among others, cytochrome P450 (CYP) 2A6 and 2B6 enzymes were implemented, including kinetics for CYP2A6 poor metabolizers. Results The model is able to precisely describe and predict both nicotine plasma and brain tissue concentrations, cotinine plasma concentrations, and heart rate profiles. 100% of the predicted area under the concentration-time curve (AUC) and maximum concentration (C max) values meet the twofold acceptance criterion with overall geometric mean fold errors of 1.12 and 1.15, respectively. The administration of combustible cigarettes, e-cigarettes, nicotine patches, and nicotine gums was successfully implemented in the model and used to identify differences in steady-state nicotine brain tissue concentration patterns. Conclusions Our PBPK/PD model may be helpful in further investigations of nicotine dependence and smoking cessation strategies. As the model represents the first nicotine PBPK/PD model predicting nicotine concentration and heart rate profiles after the use of e-cigarettes, it could also contribute to a better understanding of the recent increase in youth e-cigarette use.

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Section: (B)supporting

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Comprehensive Parent–Metabolite PBPK/PD Modeling Insights into Nicotine Replacement Therapy Strategies

et al. 2020

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“…However, an association between NMR and alcoholic drinks per month was not found in a mixed sample of smokers and non-smokers, who were all of Black-African descent (N=190) [ 156 ]. Within Caucasian males (N=22) undergoing treatment for alcohol use disorder, NMR reduced on average 50% from alcohol-detoxification week 1 through the 7 th week of treatment, despite indications that smoking rates had not changed (as indicated by no significant changes in total nicotine equivalents (TNE) in the urine) [ 157 ]. Taken together, these findings suggest that alcohol in e-cigarettes may influence nicotine effects and, if delivered chronically in sufficient levels, may influence nicotine metabolism.…”

Section: E-liquid Components and Characteristicsmentioning

confidence: 99%

E-cigarettes: Impact of E-Liquid Components and Device Characteristics on Nicotine Exposure

2018

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BackgroundElectronic cigarette (e-cigarette) use has increased substantially in recent years. While e-cigarettes have been proposed as a potentially effective smoking cessation tool, dual-use in smokers is common and e-cigarettes are widely used by non-smokers, including youth and young-adult non-smokers. Nicotine, the primary addictive component in cigarettes, is present at varying levels in many e-liquids. E-cigarettes may lead to initiation of nicotine use in adult and youth non-smokers, re-initiation of nicotine dependence in ex-smokers or increased severity of nicotine dependence in dual-users of cigarettes and e-cigarettes. As such, there are important clinical and policy implications to understanding factors impacting nicotine exposure from e-cigarettes. However, the broad and rapidly changing range of e-liquid constituents and e-cigarette hardware which could impact nicotine exposure presents a challenge. Recent changes in regulatory oversight of e-cigarettes underscore the importance of synthesizing current knowledge on common factors which may impact nicotine exposure.MethodsThis review focuses on factors which may impact nicotine exposure by changing e-cigarette use behavior, puff topography, altering the nicotine yield (amount of nicotine exiting the e-cigarette mouth piece including nicotine exhaled as vapor) or more directly by altering nicotine absorption and bioavailability.ResultsTopics reviewed include e-liquid components or characteristics including flavor additives (e.g., menthol), base e-liquid ingredients (propylene glycol, vegetable glycerin), components commonly used to dissolve flavorants (e.g., ethanol), and resulting properties of the e-liquid (e.g., pH), e-cigarette device characteristics (e.g., wattage, temperature, model) and user behavior (e.g., puff topography) which may impact nicotine exposure.ConclusionE-liquid characteristics and components, e-cigarette hardware and settings, and user behavior can all contribute substantially to nicotine exposure from e-cigarettes.

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“…3 Moreover, studies have shown a higher prevalence of cigarette smoking or drug abuse among subjects who engage in heavy or frequent binge drinking. [3][4][5] AUDs are highly comorbid with mood and anxiety disorders in adults and are associated with substantial societal and personal costs. In a study conducted by Grant et al, among adults seeking treatment for an AUD, 40.69% and 33.3% were diagnosed with at least one current comorbid mood disorder and anxiety disorder, respectively.…”

Section: Introductionmentioning

confidence: 99%

Mood disorder, anxiety, and suicide risk among subjects with alcohol abuse and/or dependence: a population-based study

Wiener

Moreira

Zago

et al. 2017

Rev. Bras. Psiquiatr.

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Objective: To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. Methods: This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores X 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). Results: Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. Conclusion: These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.Keywords: Alcohol abuse and/or dependence; anxiety; mood disorder; depression; suicide risk IntroductionAlcohol consumption is highly prevalent worldwide and has numerous negative consequences for health and quality of life, especially in the young population. 1 Alcohol use disorders (AUDs) are among the most frequently diagnosed disorders, with a 12-month prevalence rate of 8.5%. 2 In the United States alone, according to the 2013 National Survey on Drug Use and Health, 37.9% of young adults reported binge drinking (four or more drinks for women and five or more drinks for men on an occasion) at least once in the past 30 days. 3 Moreover, studies have shown a higher prevalence of cigarette smoking or drug abuse among subjects who engage in heavy or frequent binge drinking. [3][4][5] AUDs are highly comorbid with mood and anxiety disorders in adults and are associated with substantial societal and personal costs. In a study conducted by Grant et al., among adults seeking treatment for an AUD, 40.69% and 33.3% were diagnosed with at least one current comorbid mood disorder and anxiety disorder, respectively. 6 The diagnosis of current mood or anxiety disorders among individuals with AUD is challenging, because many symptoms of intoxication, for example, resemble those of mood and anxiety disorders. 7 In addition to mood disorders and anxiety, other serious problems that can develop in people with AUDs include violent behavior and suicide attempts. 8 Alcoholics are 60 to 120 times more likely to attempt suicide compared to the general population. 9 Furthermore, studies demonstrate that 85 out of every 100 individuals who complete suicide had comorbid depression and/or alcoholism. 10 Individuals with AUDs should be evaluated for the risk of suicide whenever they present with depressive symptoms, 11 Psiquiatria. 2018;40:1-5 Br...

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Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers

Cited by 28 publications

References 50 publications

Comprehensive Parent–Metabolite PBPK/PD Modeling Insights into Nicotine Replacement Therapy Strategies

Comprehensive Parent–Metabolite PBPK/PD Modeling Insights into Nicotine Replacement Therapy Strategies

E-cigarettes: Impact of E-Liquid Components and Device Characteristics on Nicotine Exposure

Mood disorder, anxiety, and suicide risk among subjects with alcohol abuse and/or dependence: a population-based study

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