Elimination kinetics of the tobacco-specific biomarker and lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is tobacco specific and has a longer half-life than other tobacco biomarkers studied thus far. An accurate measurement of the NNAL half-life is important for optimal use to assess exposure to tobacco smoke. We determined the half-life of NNAL in urine in eight daily smokers on a clinical research ward and in five occasional smokers in a real-life environment. Total NNAL in urine was monitored for 14 days in daily smokers after stopping smoking and for up to 60 days in occasional smokers. The average half-life for the terminal phase in the daily smoker group using a two-compartmental body model was 10.3 days (beta phase), and using a noncompartmental model, it was 9.1 days. In the occasional group, these values were 17.6 and 16.0 days, respectively. The alpha-phase half-lives were 14.3 and 27.8 hours for the two groups, respectively. The inter-subject coefficient of variation of the NNAL terminal half-life ranged from 14% to 30%, and the intra-subject coefficient of variation ranged from 3% to 18%. There was very good agreement between the plasma and urinary half-lives in two subjects with plasma analyses: 7.4 versus 7.9 days and 9.2 versus 10.7 days. Mean renal clearance of NNAL was 13 +/- 2.3 mL/min. The terminal half-life of NNAL of 10 to 18 days indicates that this biomarker can be used to detect tobacco smoke exposure for 6 to 12 weeks after cessation of exposure and requires a similar time to assess the steady levels of NNAL after switching from one tobacco product to another.
Goniewicz
Maciej L
ML
Department of Medicine, University of California, San Francisco, USA.
Havel
Christopher M
CM
Peng
Margaret Wilson
MW
Jacob
Peyton
P
Dempsey
Delia
D
Yu
Lisa
L
Zielinska-Danch
Wioleta
W
Koszowski
Bartosz
B
Czogala
Jan
J
Sobczak
Andrzej
A
Benowitz
Neal L
NL
D000328:Adult; D054316:Biomarkers, Pharmacological / Q000652:urine*; D002273:Carcinogens / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009602:Nitrosamines / Q000493:pharmacokinetics*; D012307:Risk Factors; D012907:Smoking; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D054316:Biomarkers, Pharmacological; D002273:Carcinogens; D009602:Nitrosamines; C051577:4-(methylnitrosoamino)-4-(3-pyridyl)-1-butanol