Nicotine metabolism involves multiple steps and several enzymatic pathways. Up to 75% of nicotine is converted to cotinine mainly by CYP2A6, 15% of nicotine is metabolized through other metabolic pathways, and a minor fraction (10–15%) is excreted to urine unchanged. The majority of cotinine is further converted to 3-hydroxycotinine exclusively by CYP2A6; up to 40% is excreted to urine as 3-hydroxycotinine while 10% is further metabolized into 3-hydroxycotinine-glucuronide by UGT enzymes prior to excretion. Approximately 15% of cotinine is converted to cotinine-glucuronide by UGT enzymes, and the remaining is metabolized through other pathways. [9]
