Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour

Tricker, Anthony R.

doi:10.1016/s0300-483x(02)00513-9

Cited by 98 publications

(70 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with a previous report, 40) nicotine was mainly excreted as cotinine, trans-3?-hydroxycotinine, and their glucuronides in the 3 subjects of group I (Fig. 4).…”

Section: Interindividual Dišerences In Cotinine Formation Andsupporting

confidence: 80%

Interindividual Variability in Nicotine Metabolism: C-Oxidation and Glucuronidation

Nakajima

Yokoi

2005

Drug Metabolism and Pharmacokinetics

View full text Add to dashboard Cite

Summary: Nicotine has roles in the addiction to smoking, replacement therapy for smoking cessation, as a potential medication for several diseases such as Parkinson's disease, Alzheimer's disease, and ulcerative colitis. The absorbed nicotine is rapidly and extensively metabolized and eliminated to urine. A major pathway of nicotine metabolism is C-oxidation to cotinine, which is catalyzed by CYP2A6 in human livers. Cotinine is subsequently metabolized to trans-3?-hydroxycotinine by CYP2A6. Nicotine and cotinine are glucuronidated to N-glucuronides mainly by UGT1A4 and partly by UGT1A9. Trans-3?-hydroxycotinine is glucuronidated to O-glucuronide mainly by UGT2B7 and partly by UGT1A9. Approximately 90z of the total nicotine uptake is eliminated as these metabolites and nicotine itself. The nicotine metabolism is an important determinant of the clearance of nicotine. Recently, advances in the understanding of the interindividual variability in nicotine metabolism have been made. There are substantial data suggesting that the large interindividual diŠerences in cotinine formation are associated with genetic polymorphisms of the CYP2A6 gene. Interethnic diŠerences have also been observed in the cotinine formation and the allele frequencies of the CYP2A6 alleles. Since the genetic polymorphisms of the CYP2A6 gene have a major impact on nicotine clearance, its relationships with smoking behavior or the risk of lung cancer have been suggested. The metabolic pathways of the glucuronidation of nicotine, cotinine, and trans-3?-hydroxycotinine in humans would be one of the causal factors for the interindividual diŠerences in nicotine metabolism. This review mainly summarizes recent results from our studies.

show abstract

“…Consistent with a previous report, 40) nicotine was mainly excreted as cotinine, trans-3?-hydroxycotinine, and their glucuronides in the 3 subjects of group I (Fig. 4).…”

Section: Interindividual Dišerences In Cotinine Formation Andsupporting

confidence: 80%

Interindividual Variability in Nicotine Metabolism: C-Oxidation and Glucuronidation

Nakajima

Yokoi

2005

Drug Metabolism and Pharmacokinetics

View full text Add to dashboard Cite

show abstract

“…Cotinine levels can be accurately measured in blood, urine, saliva and other body fluids. The half-life of cotinine in serum is 15-17 h, which allows for accurate estimation of daily tobacco-smoke exposure in randomly obtained blood specimens [49]. Serum cotinine levels correlate well with the number of cigarettes smoked and with the amount of time since a cigarette was smoked [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

“…Measurement of serum cotinine, a nicotine metabolite, is an objective surrogate for quantifying tobacco-smoke exposure [49]. Cotinine levels can be accurately measured in blood, urine, saliva and other body fluids.…”

Section: Discussionmentioning

confidence: 99%

Smoking is associated with an age-related decline in exhaled nitric oxide

Sundy

Hauswirth²,

Mervin-Blake³

et al. 2007

Eur Respir J

View full text Add to dashboard Cite

Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction (FeNO). The aim of the present study was to determine the impact of age on FeNO in otherwise healthy smokers and nonsmokers.FeNO and serum cotinine levels were measured in 994 healthy subjects aged 18-40 yrs. American Thoracic Society questionnaire data on smoking habits was used to validate serum cotinine levels as a surrogate marker for categorisation of smokers and nonsmokers in the cohort.Serum cotinine levels were a good discriminator of smokers (n599) and nonsmokers (n5895). FeNO levels were significantly lower in otherwise healthy smokers compared with nonsmokers. There was an inverse correlation of serum cotinine levels with FeNO. No correlation of age with FeNO was found in nonsmokers but an inverse correlation of FeNO with age in smokers was found. FeNO was significantly lower in smokers aged 21-40 yrs compared with nonsmokers aged 21-40 yrs, but was not lower in smokers aged 18-20 yrs compared with nonsmokers of the same age.Smoking was associated with decreased exhaled nitric oxide. The greatest smoking-related declines in exhaled nitric oxide occurred in older subjects. This suggests that smoking is associated with age-related declines in exhaled nitric oxide and justifies future mechanistic studies that address the impact of exhaled nitric oxide decline on lung function.

show abstract

“…CYP2A6 is involved in the metabolism of several nitrosamines, particularly those present in tobacco smoke (1), and is also responsible for most of the metabolism of nicotine in humans (6). The CYP2A6 gene is located on chromosome 19, at 19q13.2, in a cluster with other genes of the CYP2A sub-family (CYP2A7 and CYP2A13) and genes from other CYP2 sub-families (CYP2B6, CYP2F1) (7).…”

Section: Introductionmentioning

confidence: 99%

“…CYP genetic polymorphisms could be associated with the high degree of individual variability in the susceptibility to developing cancer and other diseases related A. Rossini et al to environmental carcinogens or endogenous compounds (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

<a name="home"></a>CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

Rossini

Lima

Rapozo

et al. 2006

Braz J Med Biol Res

View full text Add to dashboard Cite

Cytochrome P450 (CYP) is a superfamily of enzymes involved in the metabolism of endogenous compounds and xenobiotics. CYP2A6 catalyzes the oxidation of nicotine and the activation of carcinogens such as aflatoxin B1 and nitrosamines. CYP2E1 metabolizes ethanol and other low-molecular weight compounds and can also activate nitrosamines. The CYP2A6 and CYP2E1 genes are polymorphic, altering their catalytic activities and susceptibility to cancer and other diseases. A number of polymorphisms described are ethnic-dependent. In the present study, we determined the genotype and allele frequencies of the main CYP2A6 and CYP2E1 polymorphisms in a group of 289 volunteers recruited at the Central Laboratory of Hospital Universitário Pedro Ernesto. They had been residing in the city of Rio de Janeiro for at least 6 months and were divided into two groups according to skin color (white and non-white). The alleles were determined by allele specific PCR (CYP2A6 ) or by PCR-RFLP (CYP2E1). The frequencies of the CYP2A6*1B and CYP2A6*2 alleles were 0.29 and 0.02 for white individuals and 0.24 and 0.01 for non-white individuals, respectively. The CYP2A6*5 allele was not found in the population studied. Regarding the CYP2E1*5B allele, we found a frequency of 0.07 in white individuals, which was statistically different (P < 0.05) from that present in non-white individuals (0.03). CYP2E1*6 allele frequency was the same (0.08) in both groups. The frequencies of CYP2A6*1B, CYP2A6*2 and CYP2E1*6 alleles in Brazilians are similar to those found in Caucasians and African-Americans, but the frequency of the CYP2E1*5B allele is higher in Brazilians.

show abstract

Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour

Cited by 98 publications

References 113 publications

Interindividual Variability in Nicotine Metabolism: C-Oxidation and Glucuronidation

Interindividual Variability in Nicotine Metabolism: C-Oxidation and Glucuronidation

Smoking is associated with an age-related decline in exhaled nitric oxide

<a name="home"></a>CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro

Contact Info

Product

Resources

About