A pilot study of plasma caffeine concentrations in a US sample of smoker and nonsmoker volunteers.

Even though 85% of adults drink caffeinated beverages daily, very limited studies on plasma caffeine concentration in the US population have been published. Smoking induces cytochrome P450 1A2 (CYP1A2), which is the main enzyme involved in caffeine metabolism. The current naturalistic pilot study explores plasma caffeine concentrations in a US sample, and presents a mathematical model of the relationship between caffeine intake and plasma concentrations for smokers and nonsmokers. Caffeine intake and average plasma caffeine concentrations from morning (7:30-9:30 a.m.) and afternoon (2:00-4:00 p.m.) samples were studied in 69 volunteers (21 smokers and 48 nonsmokers). The mean caffeine intake obtained from caffeinated beverages was 3.02 mg/kg/day, which is similar to the intake in the US population. Almost all subjects in the present sample (99%; 95% confidence interval [CI]: 96-100) had detectable plasma caffeine concentrations. Smokers had significantly higher caffeine intake than nonsmokers. The ratio of concentration/dose of caffeine from caffeinated beverages was approximately four-fold higher in nonsmokers (1.33 kgxday/l) than in smokers (0.29 kgxday/l). According to the model, the median plasma caffeine concentration was two- to three-fold higher in nonsmokers for each level of caffeine intake. Our model improves our understanding of the interactions between caffeine and smoking. Additional studies are needed to replicate the model. This model may help epidemiologists to correct for the effects of smoking on caffeine intake and pharmacologists to screen for the activity of CYP1A2.

Total cotinine in plasma: a stable biomarker for exposure to tobacco smoke.

Determination of plasma cotinine concentration is the predominant assay employed to quantify smoking and exposure to environmental tobacco smoke in epidemiological studies. However, cotinine is biotransformed into secondary metabolites. This pilot study determined plasma concentrations of cotinine, cotinine glucuronide, 3-hydroxycotinine, and 3-hydroxycotinine glucuronide. Total cotinine concentration was determined by summation of all four metabolites. The goals of this study were (1) to explore the stability and validity of total cotinine concentration as a measure of tobacco smoking and as a measure of exposure to environmental tobacco smoke in nonsmokers, (2) to explore the stability of plasma concentrations of each of the four nicotine metabolites in smokers by performing a.m. and p.m. measures, and (3) to explore the stability of indices of glucuronidation as measures of possible markers for enzymatic activity. The subject sample included 76 white volunteers (32% smokers and 68% nonsmokers). Plasma total cotinine concentration appeared to be very stable, suggesting that total cotinine concentration may be a good measure for epidemiological studies employing a single plasma sample. Moreover, plasma total cotinine concentration also reflected exposure to environmental tobacco smoke more accurately than did plasma cotinine concentration, which would have not identified 27% of passive smokers. 3-Hydroxycotinine glucuronide and 3-hydroxycotinine plasma concentrations were almost as stable as cotinine concentrations. However, cotinine glucuronide and its indices of glucuronidation were unstable, suggesting that cotinine glucuronide undergoes deconjugation. New studies of total cotinine in plasma using more than two blood collections during the day are needed to definitively establish that it is a stable biomarker for epidemiological studies.

Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders.

This study replicates, using more refined methodology, the indications of prior studies that patients with schizophrenia show a greater frequency of tobacco smoking than patients with mood disorders. The sample included 66 patients with schizophrenia and 51 patients with a mood disorder who were admitted at a state hospital in Kentucky. The control group included 404 community subjects. Ever daily smoking was studied using logistic regression. Survival analyses of age of onset of daily smoking (AODS) were performed controlling for several variables including education level. Nicotine dependence was measured with a scale. The prevalence of ever and current daily smoking was respectively 92 and 83% for patients with schizophrenia, 78 and 65% for patients with mood disorders, and 47 and 26% for controls. Before the age of 20, the three populations appear to have a similar risk of smoking initiation. However, after the age of 20, the initiation rate of daily smoking for patients with schizophrenia was higher than in patients with a mood disorder, or controls. Among daily smokers, there were no differences in nicotine dependence between patients with schizophrenia and those with a mood disorder. Schizophrenia was associated with a greater probability of ever daily smoking than mood disorders and with higher rates of initiation of daily smoking after 20 years old.