title: CYP2A6 genotype but not age determines cotinine half-life in infants and children.
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.
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, San Francisco, California, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Dempsey
authors.forename: N C
authors.initials: NC
authors.lastname: Sambol
authors.forename: P
authors.initials: P
authors.lastname: Jacob
authors.forename: E
authors.initials: E
authors.lastname: Hoffmann
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: E
authors.initials: E
authors.lastname: Fuentes-Afflick
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D001741:Black or African American; D000367:Age Factors; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003367:Cotinine / Q000493:pharmacokinetics* / Q000652:urine; D065637:Cytochrome P-450 CYP2A6; D003903:Deuterium; D005838:Genotype; D006207:Half-Life; D006630:Hispanic or Latino; D006801:Humans; D007223:Infant; D014028:Tobacco Smoke Pollution; D044465:White People
chemical_list: D014028:Tobacco Smoke Pollution; D003903:Deuterium; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine