CYP2A6 Genotype but not Age Determines Cotinine Half-Life in Infants and Children

The formation of cotinine, the main proximate metabolite and a biomarker of nicotine exposure, is mediated primarily by cytochrome P450 (CYP)2A6. Our aim was to determine whether higher cotinine levels in young children exposed to secondhand smoke (SHS) are a result of age‐related differences in pharmacokinetics. Forty‐nine participants, aged 2–84 months, received oral deuterium‐labeled cotinine, with daily urine samples for up to 10 days for cotinine half‐life measurement. DNA from saliva was used for CYP2A6 genotyping. The estimate of half‐life using a mixed‐effect model was 17.9 h (95% confidence interval: 16.5, 19.3), similar to that reported in adults. There was no statistically significant effect of sex, race, age, or weight. Children with normal‐activity CYP2A6*1/*1 genotypes had a shorter half‐life than those with one or two reduced‐activity variant alleles. Our data suggest that higher cotinine levels in SHS‐exposed young children as compared with adults are due to greater SHS exposure rather than to different cotinine pharmacokinetics. Clinical Pharmacology & Therapeutics (2013); 94 3, 400–406. doi:10.1038/clpt.2013.114