Clinical trial NCT00330434: Effect of Ethanol and Genetic Polymorphisms on Bupropion Metabolism
Official title: Human CYP2B6: Induction by Ethanol and Polymorphisms
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Alcohol Drinking
Depression
Smoking Cessation
Attention Deficit Disorder
Keywords: Alcohol
Bupropion
Chlorzoxazone
Interaction
Induction
Depression
Smoking
Drinking
Cytochrome P450 Enzyme
CYP2B6
CYP2E1
Pharmacogenetics
Pharmacokinetics
Pharmacodynamics
Boston
Tufts University
Lead sponsor: Tufts University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2006-05-26
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts University School of Medicine
state: Massachusetts
Study officials:
affiliation: Tufts University; Chair of Department of Pharmacology and Experimental Therapeutics, Sackler School
name: David J. Greenblatt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts University, Department of Pharmacology and Experimental Therapeutics, Sackler School
name: Michael H. Court, BVsc, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.1097/00008571-200404000-00002.