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.

IMPACT:

This is probably relevant to active smoking as well.

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