Pharmacogenetics of Bupropion Metabolism

• ClinicalTrials.gov Identifier: NCT00791869
• Recruitment Status: Completed
• First Posted: November 17, 2008
• Last Update Posted: May 22, 2013
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

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
Metabolism; Pharmacokinetics

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: June 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: November 2010

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00791869
• Other Study ID Numbers: H133-31868; U01DA020830 ( U.S. NIH Grant/Contract )
• First Posted: November 17, 2008
• Last Update Posted: May 22, 2013
• Last Verified: May 2013

Keywords provided by University of California, San Francisco:

bupropion; smoking; pharmacokinetics; Pharmacokinetics of bupropion