One way of measuring nicotine metabolism is to use the nicotine metabolite ratio (NMR). The NMR is the ratio of the nicotine metabolites 3’-hydroxycotinine (3HC) to cotinine. The metabolism of cotinine to 3HC is mediated largely or entirely by CYP2A6. Since nicotine is also primarily metabolized by CYP2A6, the NMR reflects the rate of nicotine metabolism (25, 26). Cotinine levels are relatively stable throughout the day in daily smokers, and because concentrations of 3HC are formation-limited, the ratio of 3HC/cotinine also remains stable (9). The NMR reflects the rate of in-vivo nicotine clearance (27), such that the higher the NMR, the greater the nicotine clearance (28). A limitation of NMR based on cotinine and 3HC derived from nicotine in tobacco is its interpretation in intermittent smokers, who do not have stable levels of cotinine. Adolescent smokers are often opportunistic smokers and smoke intermittently. Consequently, their levels of cotinine can fluctuate considerably throughout the week and even within the day. Therefore, other methods of assessing nicotine metabolism are needed. In this study, we used administration of deuterium-labeled cotinine to more directly assess metabolism.
