Estimation of nicotine dose after low-level exposure using plasma and urine nicotine metabolites.
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.
Benowitz
Neal L
NL
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
Dains
Katherine M
KM
Dempsey
Delia
D
Yu
Lisa
L
Jacob
Peyton
P
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
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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