Cotinine Metabolism in Infants and Children

The long-term goal is to characterize developmental changes in CYP2A6 activity and nicotine and cotinine metabolism in infants and children. Our hypotheses are: * The rate of nicotine and cotinine metabolism and the level of CYP2A6 activity will increase with age throughout infancy and childhood. * The rate of cotinine glucuronidation (reflecting UGT 1A4 and 1A9 activity) will increase with age. * Cotinine clearance will be lower and cotinine half-life longer in African-Americans compared to Caucasians. * The excretion of cotinine glucuronide will be less among African-Americans compared to Caucasians. * Developmental increases in CYP2A6 will be greatest in children with wild type CYP2A6 genes, and will be lower in children who have CYP2A6 gene variants associated with reduced activity. This present study is the first step in the investigation of the above hypotheses. The primary goal of this study is to determine if there are age-related changes in cotinine clearance and validate the 3HC/COT ratio as a biomarker of cotinine clearance and half-life. This biomarker can then be used in larger studies to explore the hypotheses described above. The biomarker could also be used in epidemiologic studies of the health effects of SHS in infants and children. Primary Specific Aims: 1. Determine the following in infants and children between 2 and 84 months of age dosed with deuterium-labeled cotinine: * The clearance of cotinine * The half-life of cotinine * The volume of distribution of cotinine 2. Validate the 3HC/Cot ratio in saliva and in urine as a marker of cotinine clearance and half-life. Secondary Specific Aims: 3. Determine the effects of age on the cotinine metabolite profile in the 8-hour urine sample. 4. Determine if sulfation is a conjugation pathway for cotinine in infants and young children.