Nicotine is largely metabolized to its primary metabolite cotinine by the hepatic enzyme CYP2A6 (10). Cotinine is then metabolized to 3’-hydroxycotinine (3-HC) by the same enzyme (11). The ratio of 3-HC to cotinine has been shown to reflect the rate of nicotine metabolism and CYP2A6 activity (12). Consequently, the 3-HC:cotinine ratio has been used as a non-invasive marker of nicotine metabolism such that the higher the ratio of 3-HC:cotinine the greater the nicotine clearance (13).
