Drugs

, Volume 62, Supplement 2, pp 11–24

Pharmacokinetic Optimisation of Sustained-Release Bupropion for Smoking Cessation

  • J. Andrew Johnston
  • John Ascher
  • Robert Leadbetter
  • Virginia D. Schmith
  • Dipak K. Patel
  • Michael Durcan
  • Beth Bentley
Review Article

Abstract

Sustained-release bupropion (bupropion SR) is a unique, non-nicotine smoking cessation aid that is hypothesised to act upon neurological pathways involved in nicotine dependence. Pharmacokinetic and metabolism studies reveal that bupropion SR is metabolised by multiple pathways with no single pathway predominating. When one pathway is inhibited, others are available to compensate. Therefore, only a few clinically relevant drug-drug interactions involving bupropion SR have been observed, although the potential for interactions exists, as with any extensively metabolised drug. Population pharmacokinetic/pharmacodynamic analyses of data from patients receiving daily oral doses of 100mg, 150mg, or 300mg reveal that the anti-smoking efficacy of bupropion SR is directly related to dose. The incidences of dry mouth and insomnia were directly related to bupropion plasma concentrations while the incidence of anxiety was inversely proportional to bupropion plasma concentrations. To maximise efficacy (with an acceptable safety profile), the optimal daily dose for the majority of patients is 300mg.

References

  1. 1.
    Ulmer H, Diem G, Bischof HP, et al. Recent trends and sociodemographic distribution of cardiovascular risk factors: results from two population surveys in the Austrian WHO CINDI demonstration area. Wien Klin Wochenschr 2001; 113: 573–9PubMedGoogle Scholar
  2. 2.
    Breslau N, Johnson EO, Hiripi E, et al. Nicotine dependence in the United States: prevalence, trends, and smoking persistence. Arch Gen Psychiatry 2001; 58: 810–6PubMedCrossRefGoogle Scholar
  3. 3.
    Molarius A, Parsons RW, Dobson AJ, et al. Trends in cigarette smoking in 36 populations from the early 1980s to the mid-1990s: findings from the WHO MONICA project. Am J Public Health 2001; 91: 206–12PubMedCrossRefGoogle Scholar
  4. 4.
    Anonymous. Cigarette smoking among adults: United States, 1999. Morb Mortal Wkly Rep 2001; 50: 869–73Google Scholar
  5. 5.
    Prignot J. Towards a tobacco-free world. Monaldi Arch Chest Dis 2001; 56: 79–83PubMedGoogle Scholar
  6. 6.
    Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence: quick reference guide for clinicians. Rockville (MD): US Department of Health and Human Services. Public Health Service, 2000 OctGoogle Scholar
  7. 7.
    Balfour DJK. The pharmacology underlying pharmacotherapy for tobacco dependence: a focus on bupropion. Int J Clin Pract 2001; 55: 53–7PubMedGoogle Scholar
  8. 8.
    Ascher JA, Cole JO, Colin J-N, et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 1995; 56: 395–401PubMedGoogle Scholar
  9. 9.
    Balfour DJ, Wright AE, Benwell ME, et al. The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence. Behav Brain Res 2000; 113: 73–83PubMedCrossRefGoogle Scholar
  10. 10.
    Di Chiara G. Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 2000; 393: 295–314PubMedCrossRefGoogle Scholar
  11. 11.
    Learned-Coughlin SM, Bergstrom M, Savitcheva I, et al. Bupropion elicits significant activity at the dopamine transporter in humans: a positron emission tomography study. Poster presented at the 40th annual meeting of the American College of Neuropsychopharmacology; 2001 Dec 12, Waikoloa (Hawaii)Google Scholar
  12. 12.
    Delfs JM, Zhu Y, Druhan JP, et al. Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 2000; 403: 430–4PubMedCrossRefGoogle Scholar
  13. 13.
    Miller NS, Gold MS. A hypothesis for a common neurochemical basis for alcohol and drug disorders. Psychiatr Clin North Am 1993; 16: 105–17PubMedGoogle Scholar
  14. 14.
    Dossin O, Hanoun N, Zajac JM. Involvement of locus coeruleus projections in opiate withdrawal but not in opiate tolerance in mice. Eur J Pharmacol 1996; 25: 271–4CrossRefGoogle Scholar
  15. 15.
    Golden RN, Rudorfer MV, Sherer MA, et al. Bupropion in depression: I. biochemical effects and clinical response. Arch Gen Psychiatry 1988; 45: 139–43PubMedCrossRefGoogle Scholar
  16. 16.
    Fryer JD, Lukas RJ. Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. J Pharmacol Exp Ther 1999; 288: 88–92PubMedGoogle Scholar
  17. 17.
    Slemmer JE, Martin BR, Damaj MI. Bupropion is a nicotinic antagonist. J Pharmacol Exp Ther 2000; 295: 321–7PubMedGoogle Scholar
  18. 18.
    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: 685–91PubMedCrossRefGoogle Scholar
  19. 19.
    Holm KJ, Spencer CM. Bupropion: a review of its use in the management of smoking cessation. Drugs 2000; 59: 1007–24PubMedCrossRefGoogle Scholar
  20. 20.
    Tashkin D, Kanner R, Bailey W, et al. Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial. Lancet 2001; 357: 1571–5PubMedCrossRefGoogle Scholar
  21. 21.
    Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997; 227: 1195–202CrossRefGoogle Scholar
  22. 22.
    Shiffman S, Johnston JA, Khayrallah M, et al. The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology 2000; 148: 33–40PubMedCrossRefGoogle Scholar
  23. 23.
    Jamerson BD, Nides M, Jorenby DE, et al. Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Clin Ther 2001; 23: 744–52PubMedCrossRefGoogle Scholar
  24. 24.
    Tonstad S, Murphy M, Astbury C, et al. Effectiveness and tolerability of Zyban in smokers with cardiovascular disease — week 26 follow-up phase results [oral presentation]. European Society of Cardiology; 2001 Sep 1–5; Stockholm: abstract no. 1460Google Scholar
  25. 25.
    Dale LC, Glover ED, Sachs DPL, et al. Bupropion for smoking cessation: predictors of successful outcome. Chest 2001; 119: 1357–64PubMedCrossRefGoogle Scholar
  26. 26.
    Johnston JA, Fiedler-Kelly J, Glover ED, et al. Relationship between drug exposure and the efficacy and safety of bupropion sustained-release for smoking cessation. Nicotine Tob Res 2001; 3: 131–40PubMedCrossRefGoogle Scholar
  27. 27.
    Hays JT, Hurt RD, Rigotti NA, et al. Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation: a randomized, controlled trial. Ann Intern Med 2001; 135: 423–33PubMedGoogle Scholar
  28. 28.
    Zyban® (bupropion hydrochloride) sustained-release tablets: product information. UK: GlaxoSmithKline, 2001Google Scholar
  29. 29.
    Anonymous. Bupropion to aid smoking cessation. Drug Ther Bull 2000; 38: 73–5Google Scholar
  30. 30.
    Findlay JWA, Van Wyck Fleet J, Smith PG, et al. Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol 1981; 21: 127–35PubMedCrossRefGoogle Scholar
  31. 31.
    Goodale E, Ascher J, Batey S. Cytochrome P450 metabolism of bupropion [abstract]. J Am Geriatr Soc 1999; 49: S88Google Scholar
  32. 32.
    Hsyu PH, Singh A, Giargiari TD, et al. Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers. J Clin Pharmacol 1997; 37: 737–43PubMedGoogle Scholar
  33. 33.
    Stewart JJ, Berkel HJ, Parish RC, et al. Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender. J Clin Pharmacol 2001; 41: 770–8PubMedCrossRefGoogle Scholar
  34. 34.
    Sweet RA, Pollock BG, Kirshner M, et al. Pharmacokinetics of single- and multiple-dose bupropion in elderly patients with depression. J Clin Pharmacol 1995; 35: 876–84PubMedGoogle Scholar
  35. 35.
    Schein JR. Cigarette smoking and clinically significant drug interactions. Ann Pharmacother 1995; 29: 1139–48PubMedGoogle Scholar
  36. 36.
    DeVane CL, Laizure SC, Stewart JT, et al. Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. J Clin Psychopharmacol 1990; 10: 328–32Google Scholar
  37. 37.
    Hesse LM, Venkatakrishnan K, Court MG, et al. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 2000; 28(10): 1176–83PubMedGoogle Scholar
  38. 38.
    Ketter TA, Jenkins JB, Schroeder DH, et al. Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol 1995; 15: 327–33PubMedCrossRefGoogle Scholar
  39. 39.
    Kustra R, Corrigan B, Dunn J, et al. Lack of effect of cimetidine on the pharmacokinetics of sustained-release bupropion. J Clin Pharmacol 1999; 39: 1184–8PubMedGoogle Scholar
  40. 40.
    Odishaw J, Chen C. Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects. Pharmacotherapy 2000; 20: 1448–53PubMedCrossRefGoogle Scholar
  41. 41.
    Posner J, Bye A, Jeal S, et al. Alcohol and bupropion pharmacokinetics in healthy male volunteers. Eur J Clin Pharmacol 1984; 26: 627–30PubMedCrossRefGoogle Scholar
  42. 42.
    Goetz CG, Tanner CM, Klawans HL. Bupropion in Parkinson’s disease. Neurology 1984; 34: 1092–4PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • J. Andrew Johnston
    • 1
  • John Ascher
    • 1
  • Robert Leadbetter
    • 1
  • Virginia D. Schmith
    • 1
  • Dipak K. Patel
    • 1
  • Michael Durcan
    • 1
  • Beth Bentley
    • 1
  1. 1.GlaxoSmithKlineResearch Triangle ParkUSA
  2. 2.Innovaa ResearchLLCChapel HillUSA

Personalised recommendations