Effect of Ethanol and Genetic Polymorphisms on Bupropion Metabolism

Condition(s) targeted: Alcohol Drinking; Depression; Smoking Cessation; Attention Deficit Disorder

Intervention: Bupropion (Drug); Chlorzoxazone (Drug); Ethanol (Drug)

Phase: N/A

Status: Completed

Sponsored by: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Official(s) and/or principal investigator(s):
David J. Greenblatt, MD, Principal Investigator, Affiliation: Tufts University; Chair of Department of Pharmacology and Experimental Therapeutics, Sackler School
Michael H. Court, BVsc, PhD, Principal Investigator, Affiliation: Tufts University, Department of Pharmacology and Experimental Therapeutics, Sackler School

The two purposes of this study are

1. to determine what effect the chronic and moderate/heavy drinking of alcoholic beverages has

1. on the blood level of bupropion and chlorzoxazone and their major breakdown products in the blood and

2. on the stimulant effect of bupropion and

2. to determine what effect a normal and common (25% frequency) genetic variation of a specific liver enzyme (that breaks down bupropion) has

1. on the blood levels of bupropion and its major breakdown products in the blood and

2. on the stimulant effect of bupropion.

Two groups of volunteers will be recruited for this study:

1. volunteers who drink moderate to heavy amounts of alcohol frequently and

2. volunteers who usually do not drink alcohol.

Volunteers will NOT be asked to change their drinking (or nondrinking) habits during the study.

Official title: Human CYP2B6: Induction by Ethanol and Polymorphisms

Study design: Treatment, Non-Randomized, Open Label, Placebo Control, Parallel Assignment, Pharmacodynamics Study

Primary outcome:

Agitation

Insomnia

Minimum age: 21 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Healthy adults who are 21 - 55 years of age.

- Either 1) Moderate-to-heavy drinkers who drink on average more than 14 but less than

28 drinks per week; OR 2) adults who normally abstain from drinking alcohol.

Exclusion Criteria:

- Participants who are currently taking prescription medications (including oral

contraceptives)

- Pregnancy

- Body mass index (BMI) greater than 30

- History of seizures or eating disorders

Tufts University School of Medicine, Boston, Massachusetts 02111, United States

Related publications:

Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, Greenblatt DJ. CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos. 2000 Oct;28(10):1176-83.

Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, Greenblatt DJ, Court MH. Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics. 2004 Apr;14(4):225-38. Erratum in: Pharmacogenetics. 2005 Apr;15(4):265.

Starting date: December 2005
Ending date: April 2008
Last updated: April 7, 2008