CNS Drugs

, Volume 20, Issue 4, pp 281–291 | Cite as

Tailoring Nicotine Replacement Therapy

Rationale and Potential Approaches
Leading Article

Abstract

Nicotine replacement therapy (NRT) is an effective treatment for smoking cessation, but as with all such pharmacotherapies, the majority of smokers who use NRT products do not stop smoking or remain abstinent long term. Treatment outcome is affected by a range of individual-specific factors, as well as the pharmacokinetic profile of each NRT formulation. This has led to speculation that abstinence rates could be improved if NRT treatments were individually tailored to best match each individual’s needs and preferences. There are also populations for whom special product and dosage considerations are warranted to maximise treatment safety.

This paper reviews the rationale for NRT treatment, standard dose recommendations and recommendations for how to best match NRT treatment to the specific needs of individual smokers. We also review emerging evidence that genetic profiling may one day be a useful consideration for tailoring NRT treatment.

Notes

Acknowledgements

This work was supported by funding from the National Cancer Institute (2 R01 CA71358, Gary Swan, PI and R01 CA100341, Jennifer McClure, PI). The authors wish to thank Lisa Jack MA for her assistance with the preparation of this manuscript. The authors have no potential conflicts of interest directly relevant to the contents of this review.

References

  1. 1.
    Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence: clinical practice guidelines. Rockville (MD): United States Department of Health and Human Services. Public Health Service, 2000Google Scholar
  2. 2.
    World Health Organization. WHO evidence based recommendations on the treatment of tobacco dependence [online]. Available from URL: http://www.treatobacco.net/Guidelines/WHO_EBR.pdf [Accessed 2005 Jul 18]
  3. 3.
    Curry SJ, Ludman EJ, McClure J. Self-administered treatment for smoking cessation. J Clin Psychol 2003; 59(3): 305–19PubMedCrossRefGoogle Scholar
  4. 4.
    Hays JT, Ebbert JO. Bupropion for the treatment of tobacco dependence: guidelines for balancing risks and benefits. CNS Drugs 2003; 17(2): 71–83PubMedCrossRefGoogle Scholar
  5. 5.
    West R. Bupropion SR for smoking cessation. Expert Opin Pharmacother 2003; 4(4): 533–40PubMedCrossRefGoogle Scholar
  6. 6.
    Lancaster T, Stead LF. Self-help interventions for smoking cessation. Cochrane Database Syst Rev 2005; (3): CD001118Google Scholar
  7. 7.
    Shiffman S, Paty JA, Rohay JM, et al. The efficacy of computer-tailored smoking cessation material as a supplement to nicotine patch therapy. Drug Alcohol Depend 2001; 64(1): 35–46PubMedCrossRefGoogle Scholar
  8. 8.
    Strecher VJ. Computer-tailored smoking cessation materials: a review and discussion. Patient Educ Couns 1999; 36(2): 107–17PubMedCrossRefGoogle Scholar
  9. 9.
    Stolerman IP, Jarvis MJ. The scientific case that nicotine is addictive. Psychopharmacology 1995; 117(1): 2–10PubMedCrossRefGoogle Scholar
  10. 10.
    Benowitz NL, Perez-Stable EJ, Fong I, et al. Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 1999; 291(3): 1196–203PubMedGoogle Scholar
  11. 11.
    Balfour DJ. The neurobiology of tobacco dependence: a commentary. Respiration 2002; 69(1): 7–11PubMedCrossRefGoogle Scholar
  12. 12.
    Benowitz NL, Jacob III P, Denaro C, et al. Stable isotope studies of nicotine kinetics and bioavailability. Clin Pharmacol Ther 1991; 49(3): 270–7PubMedCrossRefGoogle Scholar
  13. 13.
    Hukkanen J, Jacob III P, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev 2005; 57(1): 79–115PubMedCrossRefGoogle Scholar
  14. 14.
    Cummings KM, Hyland A. Impact of nicotine replacement therapy on smoking behavior. Ann Rev Public Health 2005; 26: 583–99CrossRefGoogle Scholar
  15. 15.
    Balfour DJ. The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens [corrected]. Nicotine Tob Res 2004; 6(6): 899–912PubMedCrossRefGoogle Scholar
  16. 16.
    Corrigall WA. Nicotine self-administration in animals as a dependence model. Nicotine Tob Res 1999; 1(1): 11–20PubMedCrossRefGoogle Scholar
  17. 17.
    Tyndale RF. Genetics of alcohol and tobacco use in humans. Ann Med 2003; 35(2): 94–121PubMedCrossRefGoogle Scholar
  18. 18.
    Benowitz NL, Jacob III P. Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther 1994; 56(5): 483–93PubMedCrossRefGoogle Scholar
  19. 19.
    Benowitz NL, Lessov CN, Swan GE, et al. Femaile sex and oral contraceptive use accelerate nicotine metabolism. Clin Pharmacol Ther. In pressGoogle Scholar
  20. 20.
    Swan GE, Jack LM, Ward MM. Subgroups of smokers with different success rates after use of transdermal nicotine. Addiction 1997; 92(2): 207–17PubMedCrossRefGoogle Scholar
  21. 21.
    Perkins KA, Donny E, Caggiula AR. Sex differences in nicotine effects and self-administration: review of human and animal evidence. Nicotine Tob Res 1999; 1(4): 301–15PubMedCrossRefGoogle Scholar
  22. 22.
    Benowitz NL, Perez-Stable EJ, Herrera B, et al. Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese-Americans. J Natl Cancer Inst 2002; 94(2): 108–15PubMedCrossRefGoogle Scholar
  23. 23.
    Messina ES, Tyndale RF, Sellers EM. A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes. J Pharmacol Exp Ther 1997; 282(3): 1608–14PubMedGoogle Scholar
  24. 24.
    Nakajima M, Yamamoto T, Nunoya K, et al. Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metab Dispos 1996; 24(11): 1212–7PubMedGoogle Scholar
  25. 25.
    Swan GE, Benowitz NL, Lessov CN, et al. Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic influence. Pharmacogenet Genomics 2005; 15(2): 115–25PubMedCrossRefGoogle Scholar
  26. 26.
    Yamazaki H, Inoue K, Hashimoto M, et al. Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol 1999; 73(2): 65–70PubMedCrossRefGoogle Scholar
  27. 27.
    Caporaso NE, Lerman C, Audrain J, et al. Nicotine metabolism and CYP2D6 phenotype in smokers. Cancer Epidemiol Biomarkers Prev 2001; 10(3): 261–3PubMedGoogle Scholar
  28. 28.
    Cholerton S, Arpanahi A, McCracken N, et al. Poor metabolisers of nicotine and CYP2D6 polymorphism. Lancet 1994; 343(8888): 62–3PubMedCrossRefGoogle Scholar
  29. 29.
    Le Gal A, Dreano Y, Lucas D, et al. Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine, and N-nitrosobenzylmethylamine. Toxicol Lett 2003; 144(1): 77–91PubMedCrossRefGoogle Scholar
  30. 30.
    Bao Z, Su T, Ding X, et al. Metabolism of nicotine and cotinine by human cytochrome P450 2A13 (CYP2A13). 13th International Symposium on Microsomes and Drug Oxidations; 2000 Jul 10–14; StresaGoogle Scholar
  31. 31.
    Cashman JR, Park SB, Berkman CE, et al. Role of hepatic flavin-containing monooxygenase 3 in drug and chemical metabolism in adult humans. Chem Biol Interact 1995; 96(1): 33–46PubMedCrossRefGoogle Scholar
  32. 32.
    Nakajima M, Tanaka E, Kwon JT, et al. Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Drug Metab Dispos 2002; 30(12): 1484–90PubMedCrossRefGoogle Scholar
  33. 33.
    Kuehl GE, Murphy SE. N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases. Drug Metab Dispos 2003; 31(11): 1361–8PubMedCrossRefGoogle Scholar
  34. 34.
    Henningfield JE, Fant RV, Buchhalter AR, et al. Pharmacotherapy for nicotine dependence. CA Cancer J Clin 2005; 55(5): 281–99PubMedCrossRefGoogle Scholar
  35. 35.
    Medicinenet.com. Nicotine patch [online]. Available from URL: http://www.medicinemet.com/nicotine-patch/article.htm [Accessed 2006 Feb 8]
  36. 36.
    Hurt RD, Lauger GG, Offord KP, et al. Nicotine-replacement therapy with use of a transdermal nicotine patch: a randomized double-blind placebo-controlled trial. Mayo Clin Proc 1990; 65(12): 1619–23CrossRefGoogle Scholar
  37. 37.
    Hughes JR. Pharmacotherapy for smoking cessation: unvalidated assumptions, anomalies, and suggestions for future research. J Consult Clin Psychol 1993; 61(5): 751–60PubMedCrossRefGoogle Scholar
  38. 38.
    Henningfield JE, Keenan RM. Nicotine delivery kinetics and abuse liability. J Consult Clin Psychol 1993; 61(5): 743–50PubMedCrossRefGoogle Scholar
  39. 39.
    Benowitz NL. Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 1996; 36: 597–613PubMedCrossRefGoogle Scholar
  40. 40.
    Paoletti P, Fornai E, Maggiorelli F, et al. Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch. Eur Respir J 1996; 9(4): 643–51PubMedCrossRefGoogle Scholar
  41. 41.
    Pickworth WB, Fant RV, Butschky MF, et al. Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal. J Pharmacol Exp Ther 1996; 279(2): 450–6PubMedGoogle Scholar
  42. 42.
    Schneider NG, Olmstead R, Mody FV, et al. Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial. Addiction 1995; 90(12): 1671–82PubMedCrossRefGoogle Scholar
  43. 43.
    Hjalmarson A, Franzon M, Westin A, et al. Effect of nicotine nasal spray on smoking cessation. Arch Intern Med 1994; 154: 2567–72PubMedCrossRefGoogle Scholar
  44. 44.
    Schneider NG, Lunell E, Olmstead RE, et al. Clinical pharmacokinetics of nasal nicotine delivery: a review and comparison to other nicotine systems. Clin Pharmacokinet 1996; 31(1): 65–80PubMedCrossRefGoogle Scholar
  45. 45.
    Schuh KJ, Schuh LM, Henningfield JE, et al. Nicotine nasal spray and vapor inhaler: abuse liability assessment. Psychopharmacology 1997; 130(4): 352–61PubMedCrossRefGoogle Scholar
  46. 46.
    Hajek P, West R, Foulds J, et al. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 1999; 159(17): 2033–8PubMedCrossRefGoogle Scholar
  47. 47.
    Choi JH, Dresler CM, Norton MR, et al. Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res 2003; 5(5): 635–44PubMedCrossRefGoogle Scholar
  48. 48.
    Glover ED, Glover PN, Franzon M, et al. A comparison of a nicotine sublingual tablet and placebo for smoking cessation. Nicotine Tob Res 2002; 4(4): 441–50PubMedCrossRefGoogle Scholar
  49. 49.
    Silagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2004; (3): CD000146Google Scholar
  50. 50.
    Fagerstrom KO, Tejding R, Westin A, et al. Aiding reduction of smoking with nicotine replacement medications: hope for the recalcitrant smoker? Tob Control 1997; 6(4): 311–6PubMedCrossRefGoogle Scholar
  51. 51.
    West R, Hajek P, Nilsson F, et al. Individual differences in preferences for and responses to four nicotine replacement products. Psychopharmacology 2001; 153(2): 225–30PubMedCrossRefGoogle Scholar
  52. 52.
    Haustein KO. What can we do in secondary prevention of cigarette smoking? Eur J Cardiovasc Prev Rehabil 2003; 10(6): 476–85PubMedCrossRefGoogle Scholar
  53. 53.
    Hurt RD, Dale LC, Fredrickson PA, et al. Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. JAMA 1994; 271: 595–600PubMedCrossRefGoogle Scholar
  54. 54.
    Dale LC, Hurt RD, Offord KP, et al. High-dose nicotine patch therapy: percentage of replacement and smoking cessation. JAMA 1995; 274(17): 1353–8PubMedCrossRefGoogle Scholar
  55. 55.
    Fredrickson PA, Hurt RD, Lee GM, et al. High dose transdermal nicotine therapy for heavy smokers: safety, tolerability and measurement of nicotine and cotinine levels. Psychopharmacology 1995; 122(3): 215–22PubMedCrossRefGoogle Scholar
  56. 56.
    Jorenby DE, Smith SS, Fiore MC, et al. Varying nicotine patch dose and type of smoking cessation counseling. JAMA 1995; 274(17): 1347–52PubMedCrossRefGoogle Scholar
  57. 57.
    Hughes JR, Lesmes GR, Hatsukami DK, et al. Are higher doses of nicotine replacement more effective for smoking cessation? Nicot Tob Res 1999; 1(2): 169–74CrossRefGoogle Scholar
  58. 58.
    Killen JD, Fortmann SP, Davis L, et al. Do heavy smokers benefit from higher dose nicotine patch therapy? Exp Clin Psychopharmacol 1999; 7(3): 226–33PubMedCrossRefGoogle Scholar
  59. 59.
    Tonnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J 1999; 13(2): 238–46Google Scholar
  60. 60.
    Blondal T, Gudmundsson LJ, Olafsdottir I, et al. Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. BMJ 1999; 318(7179): 285–8PubMedCrossRefGoogle Scholar
  61. 61.
    Bohadana A, Nilsson F, Rasmussen T, et al. Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 2000; 160(20): 3128–34PubMedCrossRefGoogle Scholar
  62. 62.
    Kornitzer M, Boutsen M, Dramaix M, et al. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med 1995; 24(1): 41–7PubMedCrossRefGoogle Scholar
  63. 63.
    Puska P, Korhonen HJ, Vartiainen E, et al. Combined use of nicotine patch and gum compared with gum alone in smoking cessation: a clinical trial in North Karelia. Tob Control 1995; 4: 231–5CrossRefGoogle Scholar
  64. 64.
    Tonnesen P, Mikkelsen KL. Smoking cessation with four nicotine replacement regimes in a lung clinic. Eur Respir J 2000; 16(4): 717–22PubMedCrossRefGoogle Scholar
  65. 65.
    Croghan GA, Sloan JA, Croghan IT, et al. Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting. Nicotine Tob Res 2003; 5(2): 181–7PubMedCrossRefGoogle Scholar
  66. 66.
    Hand S, Edwards S, Campbell IA, et al. Controlled trial of three weeks nicotine replacement treatment in hospital patients also given advice and support. Thorax 2002; 57(8): 715–8PubMedCrossRefGoogle Scholar
  67. 67.
    Sweeney CT, Fant RV, Fagerstrom KO, et al. Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. CNS Drugs 2001; 15(6): 453–67PubMedCrossRefGoogle Scholar
  68. 68.
    West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: an update. Health Education Authority. Thorax. 2000; 55(12): 987–99PubMedCrossRefGoogle Scholar
  69. 69.
    Fiore MC, Smith SS, Jorenby DE, et al. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA 1994; 271(24): 1940–7PubMedCrossRefGoogle Scholar
  70. 70.
    Bolin LJ, Antonuccio DO, Follette WC, et al. Transdermal nicotine: the long and the short of it. Psychol Addict Behav 1999; 13: 152–6CrossRefGoogle Scholar
  71. 71.
    Stapleton JA, Russell MA, Feyerabend C, et al. Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Addiction 1995; 90(1): 31–42PubMedCrossRefGoogle Scholar
  72. 72.
    Pomerleau OF, Pomerleau CS, Marks JL, et al. Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood. J Subst Abuse Treat 2003; 24(1): 13–8PubMedCrossRefGoogle Scholar
  73. 73.
    Medioni J, Berlin I, Mallet A. Increased risk of relapse after stopping nicotine replacement therapies: a mathematical modelling approach. Addiction 2005; 100(2): 247–54PubMedCrossRefGoogle Scholar
  74. 74.
    Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999; 340(9): 685–91PubMedCrossRefGoogle Scholar
  75. 75.
    Killen JD, Robinson TN, Ammerman S, et al. Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers. J Consult Clin Psychol 2004; 72(4): 729–35PubMedCrossRefGoogle Scholar
  76. 76.
    Ford CL, Zlabek JA. Nicotine replacement therapy and cardiovascular disease. Mayo Clin Proc 2005; 80(5): 652–6PubMedCrossRefGoogle Scholar
  77. 77.
    Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease. Nicotine replacement therapy for patients with coronary artery disease. Arch Intern Med 1994; 154(9): 989–95CrossRefGoogle Scholar
  78. 78.
    Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996; 335(24): 1792–8PubMedCrossRefGoogle Scholar
  79. 79.
    Greenland S, Satterfield MH, Lanes SF. A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Saf 1998; 18(4): 297–308PubMedCrossRefGoogle Scholar
  80. 80.
    Kimmel SE, Berlin JA, Miles C, et al. Risk of acute first myocardial infarction and use of nicotine patches in a general population. J Am Coll Cardiol 2001; 37(5): 1297–302PubMedCrossRefGoogle Scholar
  81. 81.
    Ludvig J, Miner B, Eisenberg MJ. Smoking cessation in patients with coronary artery disease. Am Heart J 2005; 149(4): 565–72PubMedCrossRefGoogle Scholar
  82. 82.
    Ontario Medical Association (OMA) Health Policy Department. Rethinking stop-smoking medications: myths and facts [online]. Available from URL: http://www.oma.org/phealth/stopsmok.htm [Accessed 2005 Nov 14]
  83. 83.
    Dempsey DA, Benowitz NL. Risks and benefits of nicotine to aid smoking cessation in pregnancy. Drug Saf 2001; 24(4): 277–322PubMedCrossRefGoogle Scholar
  84. 84.
    Coleman T, Antoniak M, Britton J, et al. Recruiting pregnant smokers for a placebo-randomised controlled trial of nicotine replacement therapy. BMC Health Serv Res 2004; 4(1): 29PubMedCrossRefGoogle Scholar
  85. 85.
    Hurt RD, Croghan GA, Beede SD, et al. Nicotine patch therapy in 101 adolescent smokers: efficacy, withdrawal symptom relief, and carbon monoxide and plasma cotinine levels. Arch Pediatr Adolesc Med 2000; 154(1): 31–7PubMedGoogle Scholar
  86. 86.
    Smith TA, House Jr RF, Croghan IT, et al. Nicotine patch therapy in adolescent smokers. Pediatrics 1996; 98 (4 Pt 1): 659–67PubMedGoogle Scholar
  87. 87.
    Hanson K, Allen S, Jensen S, et al. Treatment of adolescent smokers with the nicotine patch. Nicotine Tob Res 2003; 5(4): 515–26PubMedGoogle Scholar
  88. 88.
    Moolchan ET, Robinson ML, Ernst M, et al. Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Pediatrics 2005; 115(4): E407–14PubMedCrossRefGoogle Scholar
  89. 89.
    American Psychiatric Association. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry 1996; 153(10 Suppl.): 1–31Google Scholar
  90. 90.
    Abrams DB, Niaura R, Brown RA, et al. The tobacco dependence treatment handbook: a guide to best practices. New York: The Guilford Press, 2003Google Scholar
  91. 91.
    Johnstone EC, Yudkin PL, Hey K, et al. Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch. Pharmacogenetics 2004; 14(2): 83–90PubMedCrossRefGoogle Scholar
  92. 92.
    Yudkin P, Munafo M, Hey K, et al. Effectiveness of nicotine patches in relation to genotype in women versus men: randomised controlled trial. BMJ 2004; 328(7446): 989–90PubMedCrossRefGoogle Scholar
  93. 93.
    Lerman C, Wileyto EP, Patterson F, et al. The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial. Pharmacogenomics J 2004; 4(3): 184–92PubMedCrossRefGoogle Scholar
  94. 94.
    Lerman C, Jepson C, Wileyto EP, et al. Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials [online]. Available from URL: www.nature.com/npp/journal/vaop/ncurrent/abs/1300861a.html;jsessionid=FECFD092A42AD822FBB9EF8CBB6F7611 [Accessed 2005 Nov 28]. Neuropsychopharmacology [ePub ahead of print]
  95. 95.
    Lerman C, Shields PG, Wileyto EP, et al. Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial. Health Psychol 2003; 22(5): 541–8PubMedCrossRefGoogle Scholar
  96. 96.
    Swan GE, Jack LM, Curry SJ, et al. Joint effect of dopaminergic genes on likelihood of smoking following treatment with bupropion SR. Health Psychol. In pressGoogle Scholar
  97. 97.
    Cardon LR, Idury RM, Harris TJ, et al. Testing drug response in the presence of genetic information: sampling issues for clinical trials. Pharmacogenetics 2000 Aug; 10(6): 503–10PubMedCrossRefGoogle Scholar
  98. 98.
    Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999; 286(5439): 487–91PubMedCrossRefGoogle Scholar
  99. 99.
    Flowers CR, Veenstra D. The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics 2004; 22(8): 481–93PubMedCrossRefGoogle Scholar
  100. 100.
    Xu C, Goodz S, Sellers EM, et al. CYP2A6 genetic variation and potential consequences. Adv Drug Deliv Rev 2002; 54(10): 1245–56PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Center for Health StudiesGroup Health CooperativeSeattleUSA
  2. 2.SRI InternationalCenter for Health SciencesSeattleUSA

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