Clincosm LogoSign in Get a demo

Pharmacogenetics of Bupropion Metabolism

Sponsor
University of California, San Francisco (Other)
Overall Status
Completed
CT.gov ID
NCT00791869
Collaborator
(none)
43
Enrollment
1
Location
29
Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase

    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 San Francisco General Hospital (SFGH) Clinical Research Center for a 1-day admission during which multiple blood and urine samples will be collected for pharmacokinetic analysis.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    43 participants
    Observational Model:
    Case-Only
    Time Perspective:
    Cross-Sectional
    Official Title:
    Pharmacogenetics of Bupropion Metabolism
    Study Start Date :
    Jun 1, 2008
    Actual Primary Completion Date :
    Mar 1, 2010
    Actual Study Completion Date :
    Nov 1, 2010

    Outcome Measures

    Primary Outcome Measures

    1. Area under the plasma concentration versus time curve (AUC) for bupropion [0, 4, 8, 12, 16,24 hours from steady state]

      Subjects took bupropion daily for 7 days as outpatients prior to the study day to allow them to reach steady state concentrations of bupropion and its metabolites. The time frame shown is measured from 08:00 on the morning of inpatient admission.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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 - acceptable if in remission, otherwise exclude.

    • Systemic: "Morbidly Obese" Exclude if BMI > 35

    • Diabetes: By history

    • Chronic Active Hepatitis: By history; elevated Liver Function Tests

    • 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 intravenous drug abuse, recent history of Treatment program

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 San Francisco General Hospital-Clinical Research Ward San Francisco California United States 94110

    Sponsors and Collaborators

    • University of California, San Francisco

    Investigators

    • Principal Investigator: Neal L Benowitz, MD, University of California, San Francisco

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT00791869
    Other Study ID Numbers:
    • H133-31868
    • U01DA020830
    First Posted:
    Nov 17, 2008
    Last Update Posted:
    May 22, 2013
    Last Verified:
    May 1, 2013
    Keywords provided by University of California, San Francisco
    bupropion
    smoking
    pharmacokinetics
    Pharmacokinetics of bupropion

    Study Results

    No Results Posted as of May 22, 2013