There is wide variability in cotinine levels per cigarette smoked. We hypothesized that in addition to smoking frequency, other behavioral measures of nicotine dependence, such as the time to first cigarette after waking, are associated with cotinine levels. To test this hypothesis, we measured plasma and urinary cotinine in a community-based study of 252 black and white daily cigarette smokers. Among one pack per day smokers, plasma cotinine levels varied from 16 to 1,180 ng/mL, a 74-fold difference. Two nicotine dependence phenotypes were discerned by time after waking. Subjects in the "low" dependent phenotype smoked >30 minutes after waking and nearly all smoked ≤20 cigarettes per day. Cotinine levels increased linearly with cigarette consumption in this group. Subjects in the "high" dependent phenotype smoked ≤30 minutes after waking but had a wide range in the frequency of daily cigarettes (6-70). Compared with the low dependent phenotype, there were relatively small differences in cotinine by cigarette frequency with evidence of a plateau effect in heavy smokers (∼30). After adjusting for cigarette frequency, the levels of cotinine by time to first cigarette were as follows: ≤5 minutes, 437 [95% confidence limits (CL), 380-494]; 6 to 30 minutes, 352 (95% CL, 291-413), 31 to 60 minutes, 229 (95% CL, 140-317), and >60 minutes, 215 (95% CL, 110-321). Similar findings were observed for urinary cotinine. These findings suggest that the time to first cigarette is a strong predictor of nicotine uptake and should be considered in the design of smoking interventions.
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