Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance.

Objectives: To investigate if the nicotine metabolite ratio (NMR, the ratio of nicotine metabolites 3'-hydroxycotinine/cotinine) is a reliable phenotypic biomarker for nicotine clearance across races, and as a function of differences in the rate of nicotine, cotinine and 3'-hydroxycotinine glucuronidation and UGT genotypes.

Methods: Participants [Caucasians (Whites), African Americans (Blacks) and Asian-Americans (Asians)] received an oral solution of deuterium-labeled nicotine and its metabolite cotinine. Plasma and saliva concentrations of nicotine and cotinine were used to determine oral clearances.

The influence of nicotine metabolic rate on working memory over 6 hours of abstinence from nicotine.

Background: A faster rate of nicotine metabolism has been associated with smoking more cigarettes, greater nicotine withdrawal symptoms, and lower smoking quit rates. However, the association between nicotine metabolic rate (NMR) and cognitive functioning during withdrawal has not been determined.

Methods: We compared cognitive function in 121 fast or slow nicotine metabolizers after smoking, and at 3 and 6 h of nicotine abstinence.

Effects of Nicotine Metabolic Rate on Cigarette Reinforcement.

Introduction: The rate of nicotine metabolism, estimated by the nicotine metabolite ratio (NMR), is an important determinant of tobacco dependence. This study investigated the effect of NMR on smoking behavior due to nicotine reinforcement during ad libitum smoking.

Aims And Methods: As part of a larger study, participants were stratified based on saliva NMR as fast and slow metabolizers.

Relationship between skin melanin index and nicotine pharmacokinetics in African American smokers.

Background: Blacks bear a disproportionate burden of smoking-related diseases and experience greater difficulty quitting smoking than Whites. Nicotine has a high affinity for melanin, and it has been hypothesized that melanin levels might influence nicotine pharmacokinetics and enhance dependence. The aim of this study was to evaluate the hypothesis that melanin affects nicotine disposition kinetics in humans.

Butanediol Conversion to Gamma-Hydroxybutyrate Markedly Reduced by the Alcohol Dehydrogenase Blocker Fomepizole.

1,4-Butanediol (BDO)-used as solvent and abused for its euphoric effects-is converted to gamma-hydroxybutyrate (GHB) by the enzyme alcohol dehydrogenase. This double-blind, placebo-controlled crossover study with six healthy volunteers is the first to date investigating the role of the ADH inhibitor fomepizole (4-methylpyrazole (4MP)) in moderating this conversion in humans. Participants received on two different days either intravenous placebo or 15 mg/kg 4MP followed by oral administration of 25 mg/kg BDO.

Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence.

This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (NMR), on tobacco dependence. We stratified 136 smokers on the basis of saliva NMR as fast (n = 65) and slow (n = 71) metabolizers. Two "loading cigarettes" were smoked after overnight, and a "reward cigarette" was smoked after 6 hours of daytime, abstinence.

Effect of γ-hydroxybutyrate (GHB) on driving as measured by a driving simulator.

Rationale: Gamma-hydroxybutyrate acid (GHB), a GABA receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery.

Objective: To assess effects of oral GHB (Xyrem®) upon driving as measured by a driving simulator, and to determine plasma concentrations associated with impairment and the time course of recovery.

Methods: Randomized, double-blind, two-arm crossover study, during which 16 participants received GHB 50 mg/kg orally or placebo.

Comparison of Urine 4-(Methylnitrosamino)-1-(3)Pyridyl-1-Butanol and Cotinine for Assessment of Active and Passive Smoke Exposure in Urban Adolescents.

Many adolescents are exposed to tobacco smoke, from either active smoking (CS) or secondhand smoke (SHS) exposure. Tobacco-specific biomarkers of exposure include cotinine (detects use in past 2-4 days) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; detects use for a month or longer). NNAL is expected to detect more intermittent tobacco exposure.

Nicotine Delivery and Vaping Behavior During E-cigarette Access.

Objective: To characterize vaping behavior and nicotine intake during e-cigarette access.

Methods: Thirteen adult e-cigarette users had 90 minutes of videotaped access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session.

Urine Cotinine Screening Detects Nearly Ubiquitous Tobacco Smoke Exposure in Urban Adolescents.

Introduction: Routine biochemical assessment of tobacco smoke exposure could lead to more effective interventions to reduce or prevent secondhand smoke (SHS)-related disease in adolescents. Our aim was to determine using urine cotinine (major nicotine metabolite) measurement the prevalence of tobacco smoke exposure among adolescents receiving outpatient care at an urban public hospital.

Methods: Surplus urine was collected in 466 adolescents attending pediatric or urgent care clinics at Zuckerberg San Francisco General Hospital, serving families with lower levels of income and education, in 2013-2014.

Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity.

Objective: The rate of nicotine metabolism, determined primarily by CYP2A6 activity, influences tobacco dependence and smoking-induced disease risk. The prevalence of CYP2A6 gene variants differs by race, with greater numbers in African Americans compared with Caucasians. We studied nicotine disposition kinetics and metabolism by the CYP2A6 genotype and enzymatic activity, as measured by the nicotine metabolite ratio (NMR), in African American smokers.

The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers.

Background: African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step toward decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior.

Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes.

Aims: To measure the systemic retention of nicotine, propylene glycol (PG) and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics.

Design: E-cigarette users recruited over the internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette.

Intake of toxic and carcinogenic volatile organic compounds from secondhand smoke in motor vehicles.

Background: Volatile organic compounds (VOC) from tobacco smoke are associated with cancer, cardiovascular, and respiratory diseases. The objective of this study was to characterize the exposure of nonsmokers to VOCs from secondhand smoke (SHS) in vehicles using mercapturic acid metabolites.

Methods: Fourteen nonsmokers were individually exposed in the backseat to one hour of SHS from a smoker seated in the driver's seat who smoked three cigarettes at 20-minute intervals in a stationary car with windows opened by 10 cm.

Biomarkers of secondhand smoke exposure in automobiles.

Objectives: The objectives of this study were: (1) to characterise the exposure of non-smokers exposed to secondhand smoke (SHS) in a vehicle using biomarkers, (2) to describe the time course of the biomarkers over 24 h, and (3) to examine the relationship between tobacco biomarkers and airborne concentrations of SHS markers.

Methods: Eight non-smokers were individually exposed to SHS in cars with fully open front windows and closed back windows over an hour from a smoker who smoked three cigarettes at 20 min intervals. The non-smokers sat in the back seat on the passenger side, while the smoker sat in the driver's seat.

Determination of tobacco smoke exposure by plasma cotinine levels in infants and children attending urban public hospital clinics.

OBJECTIVE To determine the prevalence of secondhand smoke (SHS) exposure among infants and young children who received preventive care at pediatric preventative care clinics associated with an urban public hospital. Cotinine, a metabolite of nicotine, has been used to study SHS exposure in population-based studies of children 3 years of age or older. DESIGN Retrospective study using a convenience sample.

Nicotine metabolism in pregnant and nonpregnant rabbits.

Smoking during pregnancy remains a major public health concern and is associated with numerous adverse effects. Recently the clearance of nicotine and cotinine was shown to be substantially increased in pregnant women compared with nonpregnant controls. The present study investigated the usefulness of the rabbit for studying the molecular basis for the observed changes in nicotine and cotinine disposition during pregnancy.

Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine spot saliva samples II. Model application.

To develop and compare methods that predict individual nicotine (NIC) clearance, which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3'-hydroxycotinine (3HC) measurements. COT and 3HC saliva concentrations in smokers were simulated utilizing a mechanistic population pharmacokinetic model of NIC metabolism that was adapted from the one described in a companion paper. Four methods to predict NIC clearance using the metabolites concentrations were compared.

Population pharmacokinetics of nicotine and its metabolites I. Model development.

We present a mechanistic population model for the pharmacokinetics of nicotine (NIC), its primary (CYP2A6-generated) metabolite cotinine (COT), and COT's primary (CYP2A6-generated) metabolite, trans-3'-hydroxycotinine (3HC). Sixty-six subjects received oral deuterium-labeled NIC (NIC-d(2), 2 mg), and COT (COT-d(4), 10 mg) simultaneously. Frequent plasma/saliva samples were taken for measurement of concentrations of NIC-d(2), COT-d(2), 3HC-d(2), COT-d(4), and 3HC-d(4).

Is exposure to cocaine or cigarette smoke during pregnancy associated with infant visual abnormalities?

The aim of this study was to assess the association between cocaine or cigarette smoke exposure in utero and visual outcome. A total of 153 healthy infants (89 males, 64 females; gestational age range 34 to 42 weeks) were prospectively enrolled in a masked, race-matched study. Quantitative analyses of urine and meconium were used to document exposure to cigarette smoke and cocaine.

Environmental tobacco smoke exposure in low-income 6-year-olds: parent report and urine cotinine measures.

We examined the prevalence and level of environmental tobacco smoke (ETS) exposure using urine cotinine levels in children and three types of maternal self-reports in a sample of 196 low socioeconomic status (SES) mothers and their children. The self-reports were report of the mother's own smoking, report of the number of household smokers, and report of the usual number of daily hours that the child was exposed to ETS. According to the reports, 59% of the children's mothers were current smokers, 71% of the children came from households with smokers, and 85% had daily exposure to ETS.