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

Clinical pharmacology and therapeutics (2013-05-30)
D A Dempsey, N C Sambol, P Jacob, E Hoffmann, R F Tyndale, E Fuentes-Afflick, N L Benowitz
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(−)-Cotinine, ≥98%
Sigma-Aldrich
Deuterium, 99.8 atom % D
Sigma-Aldrich
Deuterium, 99.96 atom % D
Supelco
(−)-Cotinine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Deuterium, 99.9 atom % D