CYP2A6 genotype but not age determines cotinine half-life in infants and children

Clin Pharmacol Ther. 2013 Sep;94(3):400-6. doi: 10.1038/clpt.2013.114. Epub 2013 May 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans
  • Age Factors
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Child
  • Child, Preschool
  • Cotinine / pharmacokinetics*
  • Cotinine / urine
  • Cytochrome P-450 CYP2A6
  • Deuterium
  • European Continental Ancestry Group
  • Genotype
  • Half-Life
  • Hispanic Americans
  • Humans
  • Infant
  • Tobacco Smoke Pollution

Substances

  • Tobacco Smoke Pollution
  • Deuterium
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6
  • Cotinine