Search

Background: The Hooked on Nicotine Checklist (HONC) has been used to assess nicotine dependence (loss of autonomy over tobacco) among adolescents. Existing HONC validation studies for non-cigarette products, such as electronic cigarettes (e-cigarettes), have generally not considered biomarkers of nicotine exposure.Methods: Within a cross-sectional sample of California (USA) high school students (total N = 1396; mean age 15.2 years; 56% female; 54% Hispanic/Latinx), self-reported past 30-day users of any tobacco (including e-cigarettes) completed a modified 10-item HONC questionnaire and provided saliva samples (N = 318 samples, including N = 234 exclusive past 30-day e-cigarette users). Samples were analyzed for cotinine using liquid chromatography-tandem mass spectrometry (lower limit of quantification: 1.0 ng/mL).Results: Across four categories of HONC score corresponding to an increasing number of reported dependence symptoms (scores: 0, 1, 2-4, 5-10), the prevalence of quantifiable salivary cotinine increased among past 30-day tobacco users (20%, 21%, 38%, 55%, respectively, P-for-trend < 0.001) and among past 30-day exclusive e-cigarette users (15%, 22%, 31%, 42%, respectively, P-for-trend = 0.001). Among participants with quantifiable cotinine levels, HONC total score and cotinine were positively correlated among past 30-day tobacco users (n = 89; Spearman rho = 0.449; P < 0.001) and past 30-day exclusive e-cigarette users (n = 49; Spearman rho = 0.520; P < 0.001). HONC score was also associated with past 30-day frequency of tobacco product use and reported use of tobacco within 30 min of waking.Conclusions: These results support the validity of HONC to assess nicotine dependence among adolescents. Dependence symptoms may be experienced at low levels of nicotine exposure. [ABSTRACT FROM AUTHOR]

Select Drug Category Nicotine/Tobacco Topic Behavioral Pharmacology Abstract Detail Clinical - Epidemiology Abstract Category Original Research Biomarkers that distinguish between types of tobacco product use are vital to identifying potentially associated health effects, as well as to inform tobacco product reviews and regulatory actions. This study measured nicotelline and anatalline, minor tobacco alkaloids associated with tobacco smoke particulate matter, in urine biospecimens from US adults who exclusively use cigarettes, smokeless tobacco (SLT), or electronic nicotine delivery system (ENDS), as well as adults who use SLT + cigarettes or ENDS + cigarettes from Wave 1 of the PATH Study. We hypothesized that the ratio of these alkaloids, and/or their ratios with other biomarkers of tobacco exposure, would differentiate types of tobacco product use. Nicotelline and anatalline were quantified by liquid chromatography tandem mass spectrometry. Receiver Operating Curve (ROC) characteristics of different biomarker ratios and Youden's J-index were used to determine the best threshold for distinguishing between use groups. The anatalline/nicotelline ratio by tobacco use group ranked highest to lowest: exclusive SLT (55.2 (95%CI: 47.2-64.5), dual SLT + cigarette (18.2 (95%CI: 13.2-25.1), exclusive cigarette (12.1 (95%CI: 10.3-14.1), dual ENDS + cigarette (10.0 (95%CI: 8.2-12.3), and exclusive ENDS (4.8 (95%CI: 3.6-6.4); p < 0.001). ROC analyses indicated the anatalline/nicotelline ratio was good at distinguishing between exclusive cigarette and SLT use (threshold= 2.9 (AUC= 0.90; Sensitivity= 89%, Specificity= 86%)), and exclusive ENDS from SLT use (threshold= 2.6 (AUC= 0.90; Sensitivity 96%, Specificity= 76%)), but not exclusive cigarette from ENDS nor dual use from single product use. Ratios of nicotelline and other biomarkers had improved sensitivity and specificity for distinguishing exclusive cigarette and ENDS (e.g., Nicotelline/Cotinine ratio threshold= 2.5, (AUC=.84; Sensitivity= 91%, Specificity= 76%)) and exclusive SLT vs. dual SLT + cigarettes (Nicotelline/NNAL ratio threshold=.84 (AUC=.82; Sensitivity= 74%, Specificity= 81%)). Anatalline and nicotelline can create biomarker ratios that distinguish between types of exclusive and dual tobacco product use. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study which examined the concentration of gamma-hydroxybutyric (GHB) acid in urine after single-dose concentration in humans which have been deemed significant in forensic testing and the management of drug overdose. GHB levels were measured by gas chromatography-mass spectrometry in urine. It was discovered that urine concentrations vary widely after oral administration of GHB to healthy young adults.

• THS exposure significantly increased pan-tumor incidence in CC mice. • THS exposure significantly reduced pan-tumor-free survival in CC mice. • Tumor susceptibility after THS exposure varied significantly across different CC strains. • Genetic background plays an important role in THS exposure-induced mouse tumorigenesis. Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about gamma-hydroxybutyrate (GHB) in urine.

Bupropion, an antidepressant and smoking cessation medication, is metabolized to hydroxybupropion (HB), an active metabolite, primarily by CYP2B6.To compare plasma concentrations of bupropion and metabolites at steady state in healthy volunteers with and without CYP2B6 genetic variants.In a genotype-guided study of 42 healthy individuals, we measured the plasma and urine concentrations of bupropion and its metabolites, HB, threohydrobupropion, and erythrohydrobupropion after 7 days of sustained-release bupropion dosing.CYP2B6∗6 and ∗18 gene variants were associated with ∼33% reduced concentrations of HB, with no effects on concentrations of bupropion or other metabolites. We could account for 50% of the variation in HB concentrations in a model including genotype and sex.As HB is active and its steady-state concentrations are more than 10 times higher than bupropion, CYP2B6 variants are likely to affect pharmacological activity. Because of the large individual variation within the genotype group, the use of therapeutic drug monitoring for dose optimization may be necessary. [ABSTRACT FROM AUTHOR]

CYP2A6 is the major enzyme involved in nicotine metabolism, yet large interindividual variations in the rate of nicotine metabolism exist within groups of individuals having the same CYP2A6 genotype. We investigated the influence of genetic variation in another potential nicotine-metabolizing enzyme, CYP2B6, and its interaction with CYP2A6, on the metabolism of nicotine.Two hundred and twelve healthy Caucasian adult twin volunteers underwent an intravenous infusion of stable isotope-labeled nicotine and its major metabolite, cotinine, for characterization of pharmacokinetic and metabolism phenotypes. Five CYP2B6 genetic polymorphisms causing amino acid substitutions (R22C, Q172 H, S259R, K262R, and R487C) were analyzed.We observed that the CYP2B6∗6 haplotype (defined as having both Q172 H and K262R variants) was associated with faster nicotine and cotinine clearance, and that such associations were more prominent among individuals having decreased-activity CYP2A6 genotypes. Statistically significant interactions between CYP2B6 and CYP2A6 genotypes were observed (P<0.003 for nicotine clearance and P<0.002 for cotinine clearance).Our results indicate that CYP2B6 genetic variation is associated with the metabolism of nicotine and cotinine among individuals with decreased CYP2A6 activity. Further investigation of the roles of CYP2B6 and the interaction between CYP2B6 and CYP2A6 genotypes in mediating nicotine dependence and tobacco-related diseases is merited. [ABSTRACT FROM AUTHOR]

To conduct a pharmacogenetic investigation of nicotine metabolism in twins. One hundred and thirty nine twin pairs [110 monozygotic (MZ) and 29 dizygotic (DZ)] underwent a 30-min infusion of stable isotope-labelled nicotine and its major metabolite, cotinine, followed by an 8-h in-hospital stay. Blood and urine samples were taken at regular intervals for analysis of nicotine, cotinine and metabolites by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry and subsequent characterization of pharmacokinetic and metabolism phenotypes. DNA was genotyped to confirm zygosity and for variation in the gene for the primary enzyme involved in nicotine metabolism, CYP2A6 (alleles tested: ∗1, ∗1×2, ∗2, ∗4, ∗7, ∗9 and ∗12). Univariate biometric analyses quantified genetic and environmental influences on each pharmacokinetic measure in the presence and absence of covariates, including measured CYP2A6 genotype. The best-fitting model identified a substantial amount of variation in the weight-adjusted rate of total clearance of nicotine attributable to additive genetic influences [59.4%, 95% confidence interval (CI)=44.7-70.7]. The majority of variation in the clearance of nicotine via the cotinine pathway was similarly genetically influenced (60.8%, 95% CI=46.9-71.5). Heritability estimates were reduced to 54.2% and 51.8%, respectively, but remained substantial after taking into account the effect of variation in CYP2A6 genotype. These results suggest the involvement of additional genetic factors (e.g. uncharacterized or novel CYP2A6 alleles as well as other genes in the metabolic pathway) that remain to be identified. [ABSTRACT FROM AUTHOR]

Develops and applies a novel liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to quantitate the various ephedra alkaloids found in dietary supplements that contain Ephedra species. Range of total ephedra alkaloid per serving; Variation in total ephedra alkaloid content from lot to lot; Observation that product inconsistency is common among some commercially available dietary supplements.

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.Methods: Forty-four Black participants were administered intravenous infusions of deuterium-labeled nicotine and cotinine. Plasma concentrations of nicotine and cotinine were measured, and pharmacokinetic parameters were estimated. The constitutive and facultative melanin indexes were measured using a dermaspectrophotometer.Results: The median constitutive melanin index was 60.7 (32.8-134.7) and the median facultative melanin index 68.1 (38.6-127.1). The mean (±SD) nicotine elimination half-life was 136 min (±33.5), clearance was 1237 mL/min (±331), and Vss was 204 L (±66), or 2.6 L/kg (±0.7). No evidence of significant differences was found in nicotine pharmacokinetic parameters by comparing participants in different melanin index quartiles (outliers with very high melanin index had similar pharmacokinetic values to others). Differences were not statistically significant when adjusted for age, BMI, sex and CYP2A6 genotype or the nicotine metabolite ratio (NMR), and no evidence of significant correlations were found between melanin (facultative or constitutive) and the pharmacokinetic parameters of nicotine or cotinine or tobacco dependence measures.Conclusions: Based on our finding in this group of Black smokers, we could not confirm the hypothesis that melanin significantly affects nicotine disposition kinetics or measures of tobacco dependence. [ABSTRACT FROM AUTHOR]