Nicotine is a naturally-occurring alkaloid found primarily in tobacco. It is most commonly absorbed from cigarette smoke. A cigarette contains 10 to 15 mg nicotine and delivers on average 1 mg nicotine to the smoker. Nicotine is also available from smokeless tobacco (snuff, chewing tobacco), pipe and cigar tobacco, waterpipe tobacco, and a variety of smoking cessation medications. Nicotine is also present in some insecticides, which may be a source of accidental or intentional poisoning.
The peak plasma nicotine concentration during smoking is 10 to 50 ng/mL with about 5 percent being protein bound. The half-life averages two hours. Approximately 80 to 90 percent of nicotine is metabolized by lung, liver, and kidney; the principal metabolite is cotinine, which has a plasma concentration that is 10-fold higher than nicotine. Cotinine has a half-life of 15 to 20 hours and is used as a biomarker of nicotine exposure .
Approximately 17 percent of nicotine is excreted unchanged in the urine. The rate of urinary excretion is pH-dependent, decreasing in an alkaline urine. Nicotine is found in the milk of lactating women, with concentrations that parallel those of plasma.
Racial differences in tobacco-related diseases are not fully explained by cigarette-smoking behavior. Despite smoking fewer cigarettes per day, blacks have higher levels of serum cotinine. A study comparing the daily intake and rate of metabolism of nicotine in black and white smokers found that the tobacco smoke and nicotine intake per cigarette was 30 percent higher in blacks, while total and nonrenal clearances of cotinine were significantly lower (by 10 to 15 percent) in blacks . Thus, both a higher nicotine intake and slower rate of cotinine metabolism account for the higher serum cotinine concentrations in blacks.
CYP2A6 gene — Interindividual variability in the plasma concentrations of nicotine and cotinine is considerable during smoking, even among individuals taking in similar doses of nicotine. Nicotine is metabolized primarily by the liver enzyme CYP2A6. A number of CYP2A6 gene variants have been described, several of which are associated with slower metabolism of nicotine. Some individuals have been described with CYP2A6 gene deletions who metabolize nicotine unusually slowly and generate little cotinine. Gene variants associated with slow metabolism are more prevalent among Asians and blacks. Genetically slow metabolizers tend to smoke fewer cigarettes per day and are able to quit smoking more easily than fast metabolizers .