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Published on: March 28, 2017
CYP2A6 genotype but not age determines cotinine half-life in infants and children
D A Dempsey1, N C Sambol, P Jacob
1Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, San Francisco, California, USA.
Abstract:
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.
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