Analysis of the possible therapeutic use of CYP2A6 inhibition with methoxsalen in smoking cessation

grantor: University of TorontoSmokers smoke to adjust their nicotine concentrations within a desired range. Since CYP2A6 is responsible for most of nicotine's metabolism to cotinine, use of a CYP2A6 inhibitor such as methoxsalen could have important implications in smoking cessation therapy by decreasing nicotine clearance, thereby, decreasing the need to smoke. CYP2A6 inhibition may also improve nicotine replacement therapy (NRT) by increasing nicotine concentrations and decreasing variation. This study showed that in smokers taking methoxsalen for 2 weeks, nicotine and nicotine/CO concentrations increased by 25% and 31% respectively when compared to placebo, but there was no change in smoking amount. In a separate study, methoxsalen increased nicotine concentrations by 24% and 52% from placebo, in abstinent smokers using the 21mg/day nicotine patch and 4mg nicotine gum respectively, but there was no significant change in interindividual variation. These results suggest that increased nicotine concentrations produced through CYP2A6 inhibition may be useful in enhancing NRT.M.Sc