Changes in the rate of nicotine metabolism across pregnancy: a longitudinal study (original) (raw)
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Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2015
Nicotine replacement therapy (NRT) helps non-pregnant smokers quit, but there is no evidence that standard dose NRT is effective in pregnancy. As nicotine metabolism increases in pregnancy, this could reduce NRT efficacy. Using the ratio of trans-3'-hydroxycotinine to cotinine, the nicotine metabolite ratio (NMR), we investigated relationships between the rate of nicotine metabolism, maternal characteristics and smoking cessation in pregnant women recruited to a randomised controlled trial of NRT. Data from 1050 pregnant smokers in the SNAP trial who were of 12-24 weeks gestation, had exhaled carbon monoxide readings of ≥8ppm at recruitment and who were randomised to NRT or placebo patches were used. Linear and logistic regression investigated associations between maternal characteristics and NMR and also between NMR and subsequent validated cessation from smoking. 662 women (63%) provided blood samples for NMR estimation. Higher NMR was associated with increased cigarette consu...
Longitudinal Influence of Pregnancy on Nicotine Metabolic Pathways
Journal of Pharmacology and Experimental Therapeutics, 2017
Nicotine metabolism increases in pregnancy, which may contribute to the difficulties that pregnant women have in quitting smoking. We aimed to determine the extent and timing of changes in nicotine metabolic pathways, including C-oxidation, N-glucuronidation, and the pregnancy-induced influences on the activity of enzymes mediating these pathways (CYP2A6 and UGT2B10, respectively). Current smoking pregnant women (n 5 47) provided a urine sample during early pregnancy (12.5 weeks), late pregnancy (28.9 weeks), and 6 months postpartum. Concentrations of urinary nicotine and metabolites were analyzed using liquid chromatography tandem mass spectrometry and compared using general linear repeated measures analyses. Nicotine C-oxidation was 1.07-fold (P 5 0.12) and 1.11-fold (P , 0.001) higher at early and late pregnancy, respectively, compared with postpartum. Nicotine N-glucuronidation was 1.33-fold (P 5 0.06) and 1.67-fold (P 5 0.003) higher at early and late pregnancy, respectively, compared with postpartum. The CYP2A6 phenotype ratio (total 39hydroxycotinine/cotinine) was significantly higher at early and late pregnancy compared with postpartum (all P , 0.05) and correlated with nicotine C-oxidation (all P , 0.001), suggesting CYP2A6 activity is induced during pregnancy. The UGT2B10 phenotype ratio (nicotine glucuronide/nicotine) was higher at early and late pregnancy compared with postpartum (P 5 0.07 and P , 0.05, respectively) and correlated with a second UGT2B10 phenotype ratio (cotinine glucuronide/cotinine) (all P , 0.001), suggesting UGT2B10 activity is induced during pregnancy. In conclusion, pregnancy-induced increases in nicotine metabolism start by 12 weeks gestation and continue as pregnancy progresses most likely due to induction of CYP2A6 and UGT2B10, resulting in potential reductions in the effectiveness of nicotine replacement therapies and an increase in metabolism of other CYP2A6 and UGT2B10 substrates during pregnancy.
Cigarette consumption and biomarkers of nicotine exposure during pregnancy and postpartum
Addiction, 2018
Background and AimsSmokers can regulate their nicotine intake by altering the number of cigarettes smoked per day (CPD) and their smoking intensity. The current study aimed to compare the utility of self‐reported CPD, total nicotine equivalents (TNE) and urinary cotinine to estimate nicotine intake during pregnancy.DesignLongitudinal smoking behavior and biomarker data were collected at early pregnancy, late pregnancy and at postpartum as part of a smoking cessation trial to examine voucher‐based incentives for decreasing smoking.SettingObstetric practices in Burlington, Vermont, United States.ParticipantsA subset of participants (n = 47) from the parent trial, recruited between December 2006 and June 2012, who provided a urine sample at each assessment during early pregnancy, late pregnancy and postpartum.MeasurementsSmoking was assessed using self‐reported CPD, TNE, TNE/CPD and urinary cotinine.FindingsPregnant smokers reported smoking 10.4 CPD at early pregnancy, 7.2 CPD at late ...
Nicotine & Tobacco Research, 2014
Background: Nicotine replacement therapy (NRT) helps smokers quit smoking, but trials indicate that there is no evidence that it is effective in pregnancy. As metabolism increases during pregnancy, NRT may deliver insufficient nicotine to alleviate withdrawal symptoms. There is mixed evidence as to what levels of cotinine are reached from nicotine exposure in pregnancy while using NRT, compared with smoking.
BMJ: British medical journal
The study of the nicotine patch in pregnancy by Berlin (1) was well conducted and powered but did not find increased smoking cessation rates compared to placebo control, in spite of attempting to correct for the inadequate nicotine dosing and poor compliance seen in previous studies. Apart from the issues raised by the authors and the accompanying editorial, (2) one possible explanation for the disappointing result is the failure to allow for the increased rate of nicotine and cotinine metabolism in pregnancy in calculating the replacement nicotine dose. The dose of nicotine replacement was based on a conversion ratio derived from a previous study of 10 men and 10 non-pregnant women. (3) In this study, 1 mg of nicotine per day was found to equate to each 12.5 ug/L of salivary cotinine. However, this formula needs to be modified for pregnancy as cotinine levels in pregnancy are significantly lower for a given dose of nicotine compared to non-pregnant populations. The clearance of nic...
Variations in cotinine levels in smokers during and after pregnancy
American Journal of Obstetrics and Gynecology, 1998
To compare the antenatal and postnatal cotinine levels in smoking women after controlling for the differences in smoking practices. STUDY DESIGN: A paired comparison of two measurements of cotinine concentration was conducted in 40 smoking women voluntarily recruited in a prenatal education program held in La Fe Hospital, Valencia, Spain, during 1990 and 1991. Cotinine concentration was assayed by gas chromatography in samples of saliva obtained during and after pregnancy. The Wilcoxon matched-pairs test and multiple linear regression analysis were used. RESULTS: The cotinine per cigarette ratio during pregnancy (median 3.53 ng/ml per cigarette) was significantly lower than the ratio in the postnatal testing (median 9.87 ng/ml per cigarette). This difference persisted after allowing for differences in reported cigarette consumption. CONCLUSION: These findings suggest that the available equivalencies between cotinine level and nicotine intake obtained from adult nonpregnant populations cannot be directly applied during pregnancy. (Am J Obstet Gynecol 1998;178:568-71.)