Cotinine metabolism pathways

Although on average about 70-80% of nicotine is metabolized via the cotinine pathway in humans, only 10-15% of nicotine absorbed by smokers appears in the urine as unchanged cotinine (Benowitz et al. 1994). Six primary metabolites of cotinine have been reported in humans 3 -hydroxycotinine (McKennis et al. 1963 Neurath et al. 1987), 5 -hydroxycotinine (also called allohydroxycotinine) (Neurath 1994), which exists in tautomeric equilibrium with the open chain derivative... 

Of note in the above study was the finding that the clearance of nicotine and the fractional conversion of nicotine to cotinine were significantly correlated (r = 0.59). This correlation suggests that cotinine is the most rapid or rate-limiting pathway for nicotine metabolism. Thus, people who metabolize nicotine via pathways other than those to cotinine are likely to have slower elimination of nicotine in general. 

C.B. Dewey Cotinine pathway of nicotine metabolism Am. Chem. Soc. Mtg. (1957). 

---