Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease

C. Lindsay Devane, Steven Laizure, Jonathan T. Stewart, Byron E. Kolts, Eugene G. Ryerson, Ronald L. Miller, Allen A. Lai

Research output: Contribution to journalArticle

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Abstract

Bupropion hydrochloride is a new monocyclic antidepressant. In humans, its disposition results in the formation of three major metabolites: the morpholinol metabolite, the erythroamino alcohol, and the threoamino alcohol metabolite. Bupropion’s disposition was monitored following a single oral 200 mg dose in eight healthy volunteers and eight age– (44.5 ± 8.4 years) and weight– (77.4 ± 6.7 kg) matched volunteers with alcoholic liver disease. This latter group is of interest because the incidence of depression is more frequent in alcoholics than in the general population, and the liver is the major route of elimination for cyclic antidepressants. The mean elimination half-life of the morpholinol metabolite was significantly prolonged in subjects with alcoholic liver disease (32.2 ± 13.5 vs. 21.1 ± 4.9 hours (p < 0.05), while the differences in bupropion (17.3 ± 8.6 hours vs. 16.5 ± 10.4 hours for healthy subjects and subjects with alcoholic liver disease, respectively), erythroamino alcohol (26.1 ± 13.3 hours vs. 29.8 ± 6.9 hours for healthy subjects and subjects with alcoholic liver disease, respectively), and threoamino alcohol (25.5 ± 8.6 hours vs. 23.4 ± 10.7 hours for healthy subjects and subjects with alcoholic liver disease, respectively) were minimal. Mean area under the plasma concentration time curves for bupropion and metabolites were increased in subjects with alcoholic liver disease; however, clear differences between means of these small groups did not emerge, probably due to the increased variability of bupropion pharmacokinetics in these subjects. As a therapeutic agent for the treatment of depression in chronic alcoholics who may consume alcohol in combination with their antidepressant therapy, the lack of sedation with bupropion could be advantageous. However, like other cyclic antidepressants, bupropion undergoes a first-pass effect, and liver dysfunction may alter the kinetics and dose-response relationship in this population. Patients with alcoholic liver disease should initially be dosed cautiously with bupropion.

Original languageEnglish (US)
Pages (from-to)328-332
Number of pages5
JournalJournal of Clinical Psychopharmacology
Volume10
Issue number5
StatePublished - Jan 1 1990

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Bupropion
Alcoholic Liver Diseases
Healthy Volunteers
Antidepressive Agents
Alcohols
Alcoholics
Public Opinion
Population
Half-Life
Liver Diseases
Volunteers
Therapeutics
Pharmacokinetics
Weights and Measures
Liver
Incidence

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Devane, C. L., Laizure, S., Stewart, J. T., Kolts, B. E., Ryerson, E. G., Miller, R. L., & Lai, A. A. (1990). Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. Journal of Clinical Psychopharmacology, 10(5), 328-332.

Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. / Devane, C. Lindsay; Laizure, Steven; Stewart, Jonathan T.; Kolts, Byron E.; Ryerson, Eugene G.; Miller, Ronald L.; Lai, Allen A.

In: Journal of Clinical Psychopharmacology, Vol. 10, No. 5, 01.01.1990, p. 328-332.

Research output: Contribution to journalArticle

Devane, CL, Laizure, S, Stewart, JT, Kolts, BE, Ryerson, EG, Miller, RL & Lai, AA 1990, 'Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease', Journal of Clinical Psychopharmacology, vol. 10, no. 5, pp. 328-332.
Devane, C. Lindsay ; Laizure, Steven ; Stewart, Jonathan T. ; Kolts, Byron E. ; Ryerson, Eugene G. ; Miller, Ronald L. ; Lai, Allen A. / Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease. In: Journal of Clinical Psychopharmacology. 1990 ; Vol. 10, No. 5. pp. 328-332.
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abstract = "Bupropion hydrochloride is a new monocyclic antidepressant. In humans, its disposition results in the formation of three major metabolites: the morpholinol metabolite, the erythroamino alcohol, and the threoamino alcohol metabolite. Bupropion’s disposition was monitored following a single oral 200 mg dose in eight healthy volunteers and eight age– (44.5 ± 8.4 years) and weight– (77.4 ± 6.7 kg) matched volunteers with alcoholic liver disease. This latter group is of interest because the incidence of depression is more frequent in alcoholics than in the general population, and the liver is the major route of elimination for cyclic antidepressants. The mean elimination half-life of the morpholinol metabolite was significantly prolonged in subjects with alcoholic liver disease (32.2 ± 13.5 vs. 21.1 ± 4.9 hours (p < 0.05), while the differences in bupropion (17.3 ± 8.6 hours vs. 16.5 ± 10.4 hours for healthy subjects and subjects with alcoholic liver disease, respectively), erythroamino alcohol (26.1 ± 13.3 hours vs. 29.8 ± 6.9 hours for healthy subjects and subjects with alcoholic liver disease, respectively), and threoamino alcohol (25.5 ± 8.6 hours vs. 23.4 ± 10.7 hours for healthy subjects and subjects with alcoholic liver disease, respectively) were minimal. Mean area under the plasma concentration time curves for bupropion and metabolites were increased in subjects with alcoholic liver disease; however, clear differences between means of these small groups did not emerge, probably due to the increased variability of bupropion pharmacokinetics in these subjects. As a therapeutic agent for the treatment of depression in chronic alcoholics who may consume alcohol in combination with their antidepressant therapy, the lack of sedation with bupropion could be advantageous. However, like other cyclic antidepressants, bupropion undergoes a first-pass effect, and liver dysfunction may alter the kinetics and dose-response relationship in this population. Patients with alcoholic liver disease should initially be dosed cautiously with bupropion.",
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