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Neal L Benowitz

Publications and source records attributed to Neal L Benowitz.

63 records · Page 4Linked to original sources
PubMed2002

Accelerated metabolism of nicotine and cotinine in pregnant smokers.

Cigarette smoking is the foremost modifiable risk factor for adverse pregnancy outcomes. Nicotine is a suspected fetal neuroteratogen. There is concern that nicotine may achieve toxic levels during pregnancy if nicotine replacement therapies are prescribed at doses used in the nonpregnant state. Ten healthy, volunteer, pregnant smokers received infusions of deuterium-labeled nicotine and cotinine during pregnancy and again postpartum. From blood and urine measurements, the following were determined: clearance (renal and nonrenal) of nicotine and cotinine, clearance of nicotine via the cotinine pathway (an indicator of CYP2A6 activity), and daily intake of nicotine from smoking. The clearance of nicotine and cotinine was significantly higher (60 and 140%, respectively), and the half-life of cotinine was much shorter (8.8 versus 16.6 h, P < 0.01) during pregnancy. Although plasma levels of cotinine were lower during pregnancy (119 versus 202 ng/ml, P < 0.05), daily intake of nicotine from smoking was similar during pregnancy and postpartum. For a given level of intake, the pharmacologic and toxicologic effects of nicotine during pregnancy are anticipated to be less than expected from nicotine metabolism data in nonpregnant women. Our data indicate that no downward dose adjustment needs to be made for nicotine replacement therapy during pregnancy. Conversely, higher than usual doses of nicotine may be necessary to optimize efficacy. Lower cotinine levels observed during pregnancy do not necessarily reflect less smoke exposure, and cut-off levels used to classify nonsmokers, passive smokers, and active smokers need to be established for pregnancy.

Adult↗
PubMed2002

Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking.

The purpose of this study was to compare circadian blood pressure and heart rate patterns and other cardiovascular effects of nicotine delivered rapidly (via nasal spray, NNS), slowly (transdermal nicotine, TDN), by cigarette smoking (rapid delivery of nicotine plus other smoke toxins), and placebo NNS. Twelve healthy cigarette smokers were studied on a research ward when they smoked cigarettes (16 per day) or used TDN (15 mg/16 h), NNS (24 1-mg doses per day), or placebo NNS, each for 5 days. There were no significant differences in systolic blood pressure, but diastolic blood pressure was slightly increased during cigarette smoking. Plasma epinephrine, beta-thromboglobulin, and fibrinogen levels were higher during cigarette smoking than with TDN. For most measurements, NNS values were intermediate between and not significantly different from those of cigarette smoking and TDN. We conclude that, at recommended doses, TDN and NNS have fewer effects on biomarkers of cardiovascular risk than does cigarette smoking.

Administration, Intranasal↗
PubMed2002

Maternal smoking during pregnancy and severe antisocial behavior in offspring: a review.

OBJECTIVES: Recent research suggests that in utero exposure to maternal smoking is a risk factor for conduct disorder and delinquency. We review evidence of causality, a controversial but important public health question. METHODS: We analyzed studies of maternal prenatal smoking and offspring antisocial behavior within a causal framework. RESULTS: The association is (1) independent of confounders, (2) present across diverse contexts, and (3) consistent with basic science. Methodological limitations of existing studies preclude causal conclusions. CONCLUSIONS: Existing evidence provides consistent support for, but not proof of, an etiologic role for prenatal smoking in the onset of antisocial behavior. The possibility of identifying a preventable prenatal risk factor for a serious mental disorder makes further research on this topic important for public health.

Adolescent↗
PubMed2002

Anabasine and anatabine as biomarkers for tobacco use during nicotine replacement therapy.

In this study we determined urine concentration of the tobacco alkaloids anabasine and anatabine, nicotine and its metabolites cotinine, and nornicotine in 99 cigarette smokers and 205 smokeless tobacco users. We also investigated the possibility that anabasine and anatabine can be used as biomarkers for tobacco use during nicotine replacement therapy. Urine samples and data on self-reported tobacco use were obtained from subjects enrolled in tobacco cessation programs. Urine concentrations of tobacco alkaloids and metabolites were measured and correlated with self-reported tobacco use. Concentrations of anabasine and anatabine were used to validate abstinence in smokeless tobacco users who used nicotine gum as part of the therapy. Correlations of alkaloid concentration with self-reported tobacco use before treatment ranged from fair to poor. In subjects abstaining from smokeless tobacco but using nicotine gum, anabasine and anatabine levels were below the cut-point of 2 ng/ml despite high concentrations of nicotine and cotinine resulting from nicotine gum use. Anabasine and anatabine concentrations in urine can be used to validate abstinence or measure the extent of tobacco use in persons undergoing nicotine replacement therapy.

Adult↗
PubMedDate not supplied

Within-subject variation of the salivary 3HC/COT ratio in regular daily smokers: prospects for estimating CYP2A6 enzyme activity in large-scale surveys of nicotine metabolic rate.

Nicotine is the major addictive compound in tobacco and is responsible for tobacco dependence. It is primarily metabolized to cotinine (COT) and trans-3'-hydroxycotinine (3HC) by the liver enzyme cytochrome P-450 2A6 (CYP2A6). The 3HC/COT ratio measured in the saliva of smokers is highly correlated with the intrinsic hepatic clearance of nicotine and, therefore, may be a useful non-invasive marker of CYP2A6 activity and metabolic rate of nicotine. This study assessed within-subject variation in salivary 3HC/COT ratios in six regular daily smokers. Our data provide evidence that 1. variation in the 3HC/COT ratio is not dependent on the time of sampling during the day (i.e., morning vs. night ) (P > 0.1) and 2. the average within-subject biological variation in the 3HC/COT ratio is approximately 26%. These findings should be useful for designing large-scale population surveys to assess the variation in the metabolic rate of nicotine (via CYP2A6) in smokers.

Analysis of Variance↗
PubMedDate not supplied

Caffeine-herbal ephedra combination increases resting energy expenditure, heart rate and blood pressure.

1. The purpose of the present study was to determine whether the consumption of an acute dose of caffeine and Ma Huang increases resting energy expenditure (REE), heart rate (HR) and blood pressure (BP) over a 3 h period. 2. A randomized, double-blind cross-over study was performed evaluating the acute effects of caffeine (150 mg)/herbal ephedra (Ma Huang; 20 mg ephedra alkaloids) versus a placebo. A total of eight healthy subjects (four males and four females) with a mean (+/-SD) age of 23.4+/-0.8 years (mean ages for males and females: 25.3+/-0.7 and 22.0+/-0.7 years, respectively) and 22.5+/-3.1% body fat (15.7+/-1.2 and 27.6+/-3.5% body fat for males and females, respectively) were recruited to the study. Participants were moderate caffeine users (approximately 150-300 mg/day). 3. Subjects reported to the laboratory following a 12 h fast and 48 h of a caffeine-free diet. Resting energy expenditure was measured prior to supplementation and for 15 min every 30 min for 3 h following supplementation. Heart rate and BP were obtained every 15 min. Blood samples were obtained every 30 min following the measurement of REE and analysed for caffeine, ephedrine, free fatty acids and glucose. 4. By 3 h, HR was 22.7+/-5.5% higher (P<0.05) than baseline for the caffeine/ephedra trial compared with 8.9+/-2.2% higher for the placebo group. At 3 h, systolic BP was 9.1+/-2.2% higher (P<0.05) than baseline for the caffeine/ephedra trial compared with only 1.9+/-2.9% different from baseline for the placebo trial. There was no effect of the caffeine/ephedra combination on diastolic BP. Resting energy expenditure during the last 30 min was 4.5+/-2.5% higher in the placebo trial and 10.7+/-2.5% higher (P<0.05) in the caffeine/ephedra trial; REE was 8.5 +/- 2.0% higher (P<0.05) in the caffeine/ephedra trial compared with the placebo trial. Free fatty acids increased over time in the placebo and caffeine/ephedra trials (from 0.5+/-0.05 to 0.63+/-0.05 mEq/L and from 0.48+/-0.06L to 0.8+/-0.05 mEq/L, respectively). 5. Caffeine and herbal ephedra, at doses of 150 mg and 20 mg (ephedrine), respectively, result in a significant elevation in REE, HR and BP. Although significant, the increase in energy expenditure is negligible in terms of weight loss.

Adult↗