Pharmacogenetics of Bupropion Metabolism

May 20, 2013 updated by: University of California, San Francisco

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Healthy subjects with selected CYP2B6 genotypes.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) for bupropion Time Frame: 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.	0, 4, 8, 12, 16,24 hours from steady state

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

November 14, 2008

First Submitted That Met QC Criteria