The role of the CYP2B6 enzyme in nicotine metabolism is unclear. There is some evidence for a small role in the metabolism of nicotine to cotinine (Dicke et al. 2005; Yamazaki et al. 1999). CYP2B6 may contribute to nicotine metabolism that is not mediated by CYP2A6 (Messina et al. 1997). The CYP2B6*6 haplotype (Q172H and K262R variants) is associated with faster nicotine and cotinine clearance (Benowitz et al. 2006b; Ring et al. 2007) and the CYP2B6*4 allele is associated with higher 3-HC/cotinine ratios (Johnstone et al. 2006) among individuals with reduced CYP2A6 activity.