Stable isotope studies of nicotine kinetics and bioavailability

Benowitz, Neal L.; Jacob, Peyton; Denaro, Charles; Jenkins, Roger A.

doi:10.1038/clpt.1991.28

Cited by 121 publications

(80 citation statements)

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“…Thus, cotinine reflects longterm, rather than recent, ETS exposure (Rosenberg et al, 1980). Benowitz et al (1991) reported that cotinine has limited use as a biomarker because the metabolism of cotinine differs among individuals and because there is no standard analysis method. However, cotinine has been used as a biomarker for direct and passive smokers' nicotine intake because of its consistently high sensitivity and specificity (Baranowski et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence

Kim

Lim

Lee

et al. 2004

J Expo Sci Environ Epidemiol

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Studies of the health effects of environmental tobacco smoke (ETS) using measured air concentrations are subject to bias. Cotinine, a nicotine metabolite detected in urine, has been recommended as a quantitative measure of nicotine intake and thus as a marker for ETS exposure in humans. The aim of this study was to correlate home indoor ETS levels with passive smokers' urinary cotinine levels. The urinary cotinine concentrations of 57 non-smoking women who spend 419 h a day at home and the nicotine levels in their living room air were measured over a period of 24 h. Nicotine and urinary cotinine levels were analyzed using GC/MS and HPLC/UV, respectively. In addition, information was collected regarding the smoking habits of the subjects' families. A significant correlation was found between the nicotine levels in indoor air and the urinary cotinine to creatinine ratio of the passive smokers. The smoking habits of the subjects' family members were also correlated to the urinary cotinine levels of the passive smokers.

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Section: Discussionmentioning

confidence: 99%

Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence

Kim

Lim

Lee

et al. 2004

J Expo Sci Environ Epidemiol

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“…The usual systemic absorption of nicotine from a cigarette is 1-1.5 mg but can be as high as three milligrams per cigarette with very intense smoking. 6 In experimental studies in which cigarette smoking is measured and in which nicotine and cotinine pharmacokinetic parameters are characterized, the typical cotinine concentration per cigarette is 12 ng/mL. 5 Assuming this refl ects an intake of one milligram of nicotine, one can estimate a cotinine level of 36 ng/mL for a person taking in 3 mg nicotine from each cigarette.…”

Section: Methodsmentioning

confidence: 99%

Determinants of salivary cotinine level: a population-based study in Brazil

Figueiredo

Szklo²,

Szklo

et al. 2007

Rev. Saúde Pública

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Determinantes dos níveis de cotinina salivar: um estudo de base populacional no Brasil ABSTRACT OBJECTIVE: A cross-sectional population-based study was conducted to assess, in active smokers, the relationship of number of cigarettes smoked and other characteristics to salivary cotinine concentrations. METHODS:A random sample of active smokers aged 15 years or older was selected using a stepwise cluster sample strategy, in the year 2000 in Rio de Janeiro, Brazil. The study included 401 subjects. Salivary cotinine concentration was determined using gas chromatography with nitrogen-phosphorus detection. A standard questionnaire was used to collect demographic and smoking behavioral data. The relation between the number of cigarettes smoked in the last 24h and cotinine level was examined by means of a nonparametric fi tting technique of robust locally weighted regression. RESULTS:Signifi cantly (p<0.05) higher adjusted mean cotinine levels were found in subjects smoking their fi rst cigarette within fi ve minutes after waking up, and in those smoking 1-20 cigarettes in the last 24h who reported inhaling more than ½ the time. In those smoking 1-20 cigarettes, the slope was signifi cantly higher for those subjects waiting for more than fi ve minutes before smoking their fi rst cigarette after waking up, and those smoking "light" cigarettes when compared with their counterparts. These heterogeneities became negligible and non-signifi cant when subjects with cotinine >40 ng/mL per cigarette were excluded. CONCLUSIONS:There was found a positive association between selfreporting smoking fi ve minutes after waking up, and inhaling more than ½ the time are consistent and higher cotinine levels. These can be markers of dependence and higher nicotine intake. Salivary cotinine proved to be a useful biomarker of recent smoking and can be used in epidemiological studies and smoking cessation programs.KEY WORDS: Smoking. Cotinine, pharmacokinetics. Cross-sectional studies.955 Rev Saúde Pública 2007;41(6):954-62 Nicotine has a short half-life and its major metabolite is cotinine. Cotinine has a half-life of 16-20 hours and is a useful indicator of nicotine intake from recent smoking. About 70% to 80% of nicotine absorbed into the blood stream is converted into cotinine. 5 Thus, measurement of cotinine in biological samples provides is an objective approach to identify recent smoking exposure. 5

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“…At this time, there is no pill form of nicotine replacement therapy because the higher doses required to overcome first-pass metabolism may cause nausea and diarrhea due to gastrointestinal irritation (Benowitz et al, 1991). Oral administration of even low doses (4 mg) of nicotine to those genetically deficient in CYP2A6 increased nicotine AUC by over 3-fold (Xu et al, 2002), suggesting that inhibition of nicotine metabolism can make nicotine orally bioavailable.…”

Section: Inhibition Of Nicotine Metabolism By Selegiline 997mentioning

confidence: 99%

Selegiline Is a Mechanism-Based Inactivator of CYP2A6 Inhibiting Nicotine Metabolism in Humans and Mice

Siu¹,

Tyndale²

2007

J Pharmacol Exp Ther

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Selegiline (L-deprenyl) is in clinical treatment trials as a potential smoking cessation drug. We investigated the affect of selegiline and its metabolites on nicotine metabolism. In mice, selegiline was a potent inhibitor of nicotine metabolism in hepatic microsomes and cDNA-expressed CYP2A5; the selegiline metabolites desmethylselegiline, L-methamphetamine, and L-amphetamine, also inhibited nicotine metabolism. Pretreatment with selegiline and desmethylselegiline increased inhibition (IC 50 ) in microsomes by 3.3-and 6.1-fold, respectively. In mice in vivo, selegiline increased AUC (90.7 Ϯ 5.8 versus 57.4 Ϯ 5.3 ng/h/ml, p Ͻ 0.05), decreased clearance (4.6 Ϯ 0.4 versus 7.3 Ϯ 0.3 ml/min, p Ͻ 0.05), and increased elimination half-life (12.5 Ϯ 6.3 versus 6.6 Ϯ 1.4 min, p Ͻ 0.05) of nicotine. In vitro, selegiline was a potent inhibitor of human nicotine metabolism in hepatic microsomes and cDNA-expressed CYP2A6; desmethylselegiline and L-amphetamine also inhibited nicotine metabolism. Selegiline preincubation increased inhibition in microsomes (3.7-fold) and CYP2A6 (14.8-fold); the K i for CYP2A6 was 4.2 M. Selegiline dose-and time-dependently inhibited nicotine metabolism by CYP2A6 (K I ϭ 15.6 Ϯ 2.7 M; k inact ϭ 0.34 Ϯ 0.04 min Ϫ1 ), and the inhibition was irreversible in the presence of NADPH, indicating that it is a mechanism-based inhibitor of CYP2A6. Thus, inhibition of mouse nicotine metabolism by selegiline was competitive in vitro and significantly increased plasma nicotine in vivo. In humans, where selegiline is both a competitive and mechanismbased inhibitor, it is likely to have even greater effects on in vivo nicotine metabolism. Our findings suggest that an additional potential mechanism of selegiline in smoking cessation is through inhibition of nicotine metabolism.

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Stable isotope studies of nicotine kinetics and bioavailability

Cited by 121 publications

References 0 publications

Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence

Relationship between environmental tobacco smoke and urinary cotinine levels in passive smokers at their residence

Determinants of salivary cotinine level: a population-based study in Brazil

Selegiline Is a Mechanism-Based Inactivator of CYP2A6 Inhibiting Nicotine Metabolism in Humans and Mice

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