Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

Assessment of exposure to secondhand smoke at outdoor bars and family restaurants in Athens, Georgia, using salivary cotinine.

Exposure to secondhand smoke (SHS) in outdoor settings is a growing public health concern due to recent indoor smoking bans. The objective of this study was to measure salivary cotinine, a metabolite of nicotine, in subjects aged 21-30 exposed to SHS outside bars and restaurants in Athens, Georgia. Nonsmokers participated during 6-hr periods in outdoor standing or seating areas of bars and restaurants where indoor smoking was banned, as well as a control outdoor location with no smokers over six weekends during the summer and early fall of 2007. Pre- and post-exposure saliva samples (N = 25 person-days at the bar site, N = 28 person-days at the restaurant site, and N = 11 person-days at the control) were collected and analyzed for cotinine. The mean change in the response, (ln(post) - ln(pre)) salivary cotinine levels, was significantly impacted by the type of site (bar, restaurant, control) (F = 5.09; d.f. = 2, 6.7; p = 0.0455). The median percent increase in salivary cotinine from pre-test to post-test was estimated to be 162%, 102%, and 16% at the bar, restaurant, and control sites, respectively, values that were significant increases at bars (t = 4.63; d.f. = 9.24; p = 0.0011) and restaurants (t = 4.33; d.f. = 4.47; p = 0.0097) but not at the control sites. On average, these pre-test to post-test increases in salivary cotinine were significantly higher at bar sites than control sites (t = 3.05; d.f. = 9.85; p = 0.0176) and at restaurant sites compared with control sites (t = 2.35; d.f. = 5.09; p = 0.0461). Nonsmokers outside restaurants and bars in Athens, Georgia, have significantly elevated salivary cotinine levels indicative of secondhand smoke exposure.