title: Systematic review of the relationship between the 3-hydroxycotinine/cotinine ratio and cigarette dependence.
abstract: BACKGROUND
  Individual differences in the rate of nicotine metabolism (RNM) could be related to dependence and success in stopping smoking. A range of studies have examined RNM measured by the ratio of trans-3'-hydroxycotinine and cotinine in body fluids (the ratio). A systematic review of this literature is needed to draw conclusions and identify gaps in evidence.
  
  
  OBJECTIVE
  The aim of this study is to review evidence on the association of the ratio to cigarette dependence and its role in individual tailoring of smoking cessation pharmacotherapy.
  
  
  RESULTS
  We reviewed 27 studies of the ratio related to its reliability, validity, and relationship to dependence. The ratio is a reasonably accurate proxy for RNM. There is little evidence that the ratio is related to questionnaire measures of dependence, though the existing data are limited and the ratio has been linked to smoking at night and to some aspects of smoking topography. The ratio is also only weakly associated with cigarette consumption. Its relationship to the severity of withdrawal symptoms seems also weak at best, but limited data exist. One study suggests the ratio predicts outcome of unaided quitting. Importantly, the ratio seems to predict responses both to NRT and bupropion, and thus could guide pharmacotherapy.
  
  
  CONCLUSIONS
  The evidence that the ratio is related to smoking behaviours and to cigarette dependence is limited, but the ratio seems to influence treatment response to two stop smoking medications. Further studies of the relationship between the ratio and cigarette dependence and trials of ratio-guided pharmacotherapy are needed.
authors: UK Centre for Tobacco Control Studies, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK. o.west@qmul.ac.uk
authors: Oliver
authors: O
authors: West
authors: Peter
authors: P
authors: Hajek
authors: Hayden
authors: H
authors: McRobbie
references: J Anal Toxicol. 2006 Jul-Aug;30(6):386-9
references: 16872570
references: Pharmacol Biochem Behav. 2009 Mar;92(1):6-11
references: 19000709
references: J Pharmacol Exp Ther. 1982 May;221(2):368-72
references: 7077531
references: Pediatrics. 2008 Sep;122(3):e643-7
references: 18762498
references: Nicotine Tob Res. 2007 Apr;9(4):493-8
references: 17454704
references: Pharmacogenet Genomics. 2005 Feb;15(2):115-25
references: 15861035
references: Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1396-400
references: 18559554
references: Drug Alcohol Depend. 2007 Jun 15;89(1):24-33
references: 17161559
references: Clin Pharmacol Ther. 2006 Jun;79(6):600-8
references: 16765148
references: Nicotine Tob Res. 2007 Nov;9 Suppl 4:S555-70
references: 18067032
references: Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3331-6
references: 19064547
references: J Pharmacol Exp Ther. 1997 Sep;282(3):1608-14
references: 9316878
references: Clin Pharmacol Ther. 1994 Nov;56(5):483-93
references: 7955812
references: Clin Pharmacol Ther. 2008 Jan;83(1):115-21
references: 17522595
references: Clin Pharmacol Ther. 2006 Oct;80(4):319-30
references: 17015050
references: Cancer Epidemiol Biomarkers Prev. 2011 Feb;20(2):234-8
references: 21212060
references: BMJ. 1993 May 15;306(6888):1308-12
references: 8518572
references: Nicotine Tob Res. 2008 Jun;10(6):1009-20
references: 18584464
references: Clin Pharmacol Ther. 2006 Nov;80(5):457-67
references: 17112802
references: Br J Addict. 1991 Sep;86(9):1119-27
references: 1932883
references: Eur J Clin Pharmacol. 2006 Jun;62(6):481-4
references: 16758265
references: Pharmacogenet Genomics. 2009 May;19(5):388-98
references: 19300303
references: Clin Pharmacol Ther. 2010 May;87(5):553-7
references: 20336063
references: Clin Pharmacol Ther. 2004 Jul;76(1):64-72
references: 15229465
references: Pharmacogenet Genomics. 2008 Jan;18(1):67-75
references: 18216723
references: Am J Epidemiol. 2007 Apr 15;165(8):901-10
references: 17322544
references: Hum Mutat. 2008 May;29(5):679-88
references: 18360915
references: Clin Pharmacol Ther. 2008 Sep;84(3):320-5
references: 18388868
references: Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1812-9
references: 17035386
references: Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1578-83
references: 19423535
references: Clin Pharmacol Ther. 2009 Jun;85(6):635-43
references: 19279561
references: Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3526-35
references: 19029401
references: Nicotine Tob Res. 2003 Oct;5(5):621-4
references: 14577978
references: J Neurogenet. 2009;23(3):252-61
references: 19169923
references: J Anal Toxicol. 2005 Oct;29(7):689-95
references: 16419402
references: Pharmacol Rev. 2005 Mar;57(1):79-115
references: 15734728
references: Addiction. 2008 Jun;103(6):893-904
references: 18190672