Nicotine metabolism among African American and white smokers: Group and intraindividual differences in glucuronidation

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Prevention of tobacco associated cancers requires effective approaches to treat nicotine addiction. Smokers adjust their level of smoking to maintain blood levels of nicotine, which are determined in part by rates of nicotine metabolism. Differences in nicotine metabolite levels have been observed between African American and white smokers, including elevated cotinine levels and decreased glucuronide conjugates. A study of adult African American and white smokers (n=95) was designed to evaluate race differences and individual variability in nicotine metabolism. Urinary and plasma metabolites were quantified at baseline and subsequently on three consecutive days while participants were confirmed abstinent and on the nicotine patch. In baseline 24-hour urine, the percent of cotinine in the glucuronide form was significantly lower among African Americans compared to whites (64% versus 83%, p=<0.005). A similar difference in glucuronidation was observed while participants were on the nicotine patch (41% versus 62%, p=<0.005), albeit the observed percent glucuronidation was decreased from baseline for both groups. Intraindividual variation in percent cotinine glucuronidation was low over 3 consecutive 24 hour periods (Avg. standard deviation = 2.4%). Only one participant had intraindividual variation of greater than 10%. Glucuronidation of nicotine was also lower among African Americans at baseline ( 52% versus 59% p=0.03) and on the patch ( 17% versus 32% p=<0.005). The ratio of the metabolites trans-3'-hydroxycotinine to cotinine ratio (hcot:cot) is increasingly being used as a measure of nicotine metabolism. Differences in cotinine glucuronidation may modulate the availability of free cotinine and therefore could affect the hcot:cot ratio. In this study however, increasing quartiles of cotinine glucuronidation trended towards higher hcot:cot ratios. In summary, African American smokers had significantly lower levels of cotinine glucuronide compared to whites. Environmental and genetic factors likely affect glucuronidation pathways of nicotine metabolism.