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.

Impact: This is probably relevant to active smoking as well.

Figure 1

Mean Plasma COT and 3HC 200 μg dose Average plasma concentrations of cotinine and trans-3′ hydroxycotinine sampled at various times of day in 12 subjects receiving 200 μg nicotine per day.

Figure 2

ALL urine metabolites (24 hr) 200 μg dose Average urine metabolites in 24 hour samples in 12 subjects receiving 200 μg nicotine per day. Analytes present at levels less than 3% of the nicotine were combined. This included nicotine N- oxide, cotinine N – oxide, nornicotine, nornicotine glucuronide, norcotinine and norcotinine glucuronide

Figure 3

Figure 3a. Urine - COT by dose (24 hr) Figure 3b. Urine - sum of nicotine metabolites by dose (24 hr) Correlations between daily dose of nicotine and urine cotinine (3a) and sum of nicotine metabolites [Nic + Nic-G + Cot + Cot-G + 3HC + 3HC-G] in 24 hour urine.

Figure 3

Figure 3a. Urine - COT by dose (24 hr) Figure 3b. Urine - sum of nicotine metabolites by dose (24 hr) Correlations between daily dose of nicotine and urine cotinine (3a) and sum of nicotine metabolites [Nic + Nic-G + Cot + Cot-G + 3HC + 3HC-G] in 24 hour urine.