Pharmacogenetics of Bupropion Metabolism - Full Text View

Sponsored by:	University of California, San Francisco
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00791869

Purpose

The aim of the investigators research is to see if variants in a particular gene (named CYP2B6) affect how the body metabolizes (breaks down) certain medications, including the drug bupropion. Bupropion is widely used in the treatment of depression and for helping people quit smoking. Genes are portions of DNA that code for particular proteins in the body. The investigators are studying the gene that codes for a protein called CYP2B6. Differences in the structure of the gene are called variants and may mean that a person metabolizes a drug faster or slower than a person with a different variant.

Condition
Metabolism Pharmacokinetics

MedlinePlus related topics: Smoking

Drug Information available for: Bupropion hydrochloride Bupropion

U.S. FDA Resources

Study Type:	Observational
Study Design:	Case-Only, Cross-Sectional
Official Title:	Pharmacogenetics of Bupropion Metabolism

Further study details as provided by University of California, San Francisco:

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment:	59
Study Start Date:	June 2008

Detailed Description:

Bupropion is widely used in the treatment of depression and for smoking cessation. It's most abundant metabolite, hydroxybupropion, may be responsible for most of the therapeutic effect of bupropion under conditions of long term dosing. Because the primary enzyme involved in metabolism of bupropion to hydroxybupropion is the liver enzyme CYP2B6, we propose to study the effect of different CYP2B6 genotypes on the metabolism of bupropion. These data will guide the use of genotypes as a surrogate for measuring drug blood levels in studying genetic determinants of outcomes for bupropion treatment.

A minimum of Forty-four subjects with 4 different CYP2B6 genotypes will participate in a 7-day study in which they take bupropion as outpatients for 6 days (to achieve steady state drug levels) and then come to the SFGH CCRC for a 1-day admission during which multiple blood and urine samples will be collected for pharmacokinetic analysis.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Healthy subjects with selected CYP2B6 genotypes.

Criteria

Inclusion Criteria:

Age: 18 - 65 years
Gender: Either
Ethnic/Racial Group: Any
Smoking Status: Both smokers and non-smokers are eligible
CYP2B6 genotype: CYP2B6 *1/*1 (11 subjects); *4, *5 and *6 alleles (11 each) [44 subjects total] Up to 15 additional subjects may be studied with genotypes that do not fall into one of the primary groups.

Exclusion Criteria:

Medical: Exclude most any chronic illness requiring regular medication.
Cardiac: History of angina or other serious heart disease; ECG abnormalities on screening.
Hypertension: screening visit BP of 150/95 or more after 5 min rest
Respiratory: Asthma - OK if in remission, otherwise exclude.
Systemic: "Morbidly Obese" Exclude if BMI > 35
Diabetes: By history
Chronic Active Hepatitis: By history; elevated LFT's
Cancers: By history
Pregnancy/breastfeeding: By history; positive urine pregnancy test
Seizures: individuals with a history of seizures will be excluded (risk factor for bupropion-induced seizures)
Eating Disorders: individuals with a history of eating disorders will be excluded (risk factor for bupropion-induced seizures)
Head Trauma: individuals with a history of head trauma will be excluded (risk factor for bupropion-induced seizures)
Other tobacco users (pipe, cigar, chewing tobacco, snuff users
Medications/Supplements: General Exclusion = "any regular oral and/or prescription drug use"; current use of oral contraceptives or other female hormones.
Drug/alcohol use: no alcohol abuse by history, no regular recreational drug use, any IVDA, recent hx of Tx program

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791869

Locations

United States, California
San Francisco General Hospital-Clinical Research Ward
San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

More Information

Responsible Party:	University of California, San Francisco ( Neal Benowitz, MD )
Study ID Numbers:	H133-31868, U01 DA020830
Study First Received:	November 14, 2008
Last Updated:	November 14, 2008
ClinicalTrials.gov Identifier:	NCT00791869
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:

bupropion
smoking
pharmacokinetics
Pharmacokinetics of bupropion

Study placed in the following topic categories:

Smoking
Dopamine
Bupropion

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Physiological Effects of Drugs

Psychotropic Drugs
Dopamine Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Pharmacologic Actions
Antidepressive Agents

ClinicalTrials.gov processed this record on January 16, 2009