The elimination half-life of nicotine is around 2 h. Among several nicotine metabolites, the major metabolite is cotinine. In humans, 70–80% of nicotine is converted to cotinine, mediated largely by the liver enzyme cytochrome P450 CYP2A6. Approximately 33–40% of cotinine is converted to its primary metabolite, 3′-hydroxycotinine (3HC), also by CYP2A6. Cotinine and 3′-hydroxycotinine are metabolized at a much slower rate than nicotine, and their rates of elimination are not significantly affected by changes in liver blood flow (Hukkanen et al. 2005; Mwenifumbo and Tyndale 2007).
