Pharmacogenetics of Bupropion Metabolism

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00791869
First received: November 14, 2008
Last updated: May 20, 2013
Last verified: May 2013
  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

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC) for bupropion [ Time Frame: 0, 4, 8, 12, 16,24 hours from steady state ] [ Designated as safety issue: No ]
    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.


Enrollment: 43
Study Start Date: June 2008
Study Completion Date: November 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
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.

  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 - 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: Neal L Benowitz, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00791869     History of Changes
Other Study ID Numbers: H133-31868, U01 DA020830
Study First Received: November 14, 2008
Last Updated: May 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
bupropion
smoking
pharmacokinetics
Pharmacokinetics of bupropion

Additional relevant MeSH terms:
Bupropion
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014