title: Estimation of nicotine dose after low-level exposure using plasma and urine nicotine metabolites.
abstract: BACKGROUND
  We sought to determine the optimal plasma and urine nicotine metabolites, alone or in combination, to estimate the systemic dose of nicotine after low-level exposure.
  
  
  METHODS
  We dosed 36 nonsmokers with 100, 200, or 400 microg p.o. of deuterium-labeled nicotine (doses similar to exposure to secondhand smoke) daily for 5 days and then measured plasma and urine nicotine metabolites at various intervals over 24 hours.
  
  
  RESULTS
  The strongest correlations with nicotine dose were seen for the sum of four (cotinine+cotinine-glucuronide+trans-3'-hydroxycotinine+3HC-glucuronide) or six (including also nicotine+nicotine-glucuronide) of the major nicotine metabolites in 24-hour urine collection (r=0.96), with lesser correlations for these metabolites using spot urines corrected for creatinine at various times of day (r=0.72-0.80). The sum of plasma cotinine+trans-3'-hydroxycotine was more highly correlated with nicotine dose than plasma cotinine alone (r=0.82 versus 0.75).
  
  
  CONCLUSIONS
  Our results provide guidance for the selection of biomarkers to estimate the dose of nicotine taken in low-level (secondhand smoke) tobacco exposure.
  
  
  CONCLUSIONS
  This is probably relevant to active smoking as well.
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, and Department of Medicine, University of California, San Francisco, Box 1220, San Francisco, CA 94143-1220, USA. NBenowitz@MedSFGH.ucsf.edu
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Dains
authors.forename: Delia
authors.initials: D
authors.lastname: Dempsey
authors.forename: Lisa
authors.initials: L
authors.lastname: Yu
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D003367:Cotinine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005965:Glucuronates / Q000097:blood / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D012907:Smoking / Q000378:metabolism*; D014028:Tobacco Smoke Pollution / Q000032:analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005965:Glucuronates; D014028:Tobacco Smoke Pollution; C075991:cotinine N-glucuronide; C085795:nicotine N-glucuronide; C001381:hydroxycotinine; D009538:Nicotine; D003367:Cotinine
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