Nicotine chemistry, metabolism, kinetics and biomarkers

Abstract

Nicotine underlies tobacco addiction, influences tobacco use patterns, and is used as a pharmacological aid to smoking cessation. The absorption, distribution and disposition characteristics of nicotine from tobacco and medicinal products are reviewed. Nicotine is metabolized primarily by the liver enzymes CYP2A6, UDPglucuronosyltransferase (UGT), and flavin-containing monooxygenase (FMO). In addition to genetic factors, nicotine metabolism is influenced by diet and meals, age, sex, use of estrogen-containing hormone preparations, pregnancy and kidney disease, other medications, and smoking itself. Substantial racial/ethnic differences are observed in nicotine metabolism, which are likely influenced by both genetic and environmental factors. The most widely used biomarker of nicotine intake is cotinine, which may be measured in blood, urine, saliva, hair, or nails. The current optimal plasma cotinine cut-point to distinguish smokers from non-smokers in the general US population is 3 ng ml(-1). This cut-point is much lower than that established 20 years ago, reflecting less secondhand smoke exposure due to clear air policies and more light or occasional smoking.

Fig. 1

Structures of tobacco alkaloids. Reprinted from Benowitz and Jacob (1998) with permission of Wiley-Liss, a subsidiary of Wiley

Fig. 2

Blood nicotine concentrations during and after cigarette smoking for 9 min, oral snuff (2.5 g), chewing tobacco (average 7.9 g), and nicotine gum (two 2-mg pieces). Average values for 10 subjects (±SEM). Reprinted from Benowitz et al. (1988) with permission from American Society for Clinical Pharmacology and Therapeutics

Fig. 3

Pathways of nicotine metabolism. Reprinted with permission from Hukkanen et al. 2005c

Fig. 4

Quantitative scheme of nicotine metabolism, based on estimates of average excretion of metabolites as percent of total urinary nicotine. Reprinted with permission from Hukkanen et al. 2005c