Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns
Condition: Depression
MeSH terms: Depression
Intervention: generic bupropion
Intervention description: We are comparing different formulations of bupropion that release this drug at different rates. The abbreviation IR75 means immediate release and the number is the dose in mg. The other abbreviations represent SR for sustained-release and XL for extended release, which release the drug slower than the IR formulation.
Intervention MeSH terms: Bupropion
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 34.0
Sex: All
Minimum age: 25 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The objectives of this project are to determine if the bioavailability and release pattern of
      bupropion HCl products differ and if the genotype of the metabolic enzymes affects the
      saturation of intestinal enzymes with different dose strengths within one product line.
      Findings from this project will help the FDA Center for Drug Evaluation and Research's (CDER)
      Office of Generic Drugs improve policy development and review practice in the future for
      similar products, e.g. extended release oral drug products being metabolized in the gut wall
      and having multiple strengths.

      Aim 1: To compare the pharmacokinetics of bupropion and its metabolites in plasma in healthy
      individuals when they ingest different strengths of bupropion (75-300 mg) with variable
      release profiles (IR vs XL vs SR) in GI tract.

      Working hypothesis: Variation in release rate and mechanism of bupropion formulations in
      gastrointestinal (GI) tract will impact metabolism and saturation of bupropion in GI tract,
      which will generate different concentration of bupropion and its metabolites in plasma.

      Aim 2: To investigate pharmacogenomics of CYP 2B6 that influences metabolism, saturation, and
      pharmacokinetics of bupropion

      Working hypothesis: The gain of function of CYP2B6 variants (allele *4 and *22) in patients
      will increase the metabolism of bupropion in the GI tract and liver, reduce both local
      concentration and plasma concentration of bupropion, and thus cause non-bioequivalence when
      bupropion is released earlier in GI tract
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy volunteers 25 to 55 years old.

          -  Volunteers have a Body Mass Index (BMI), calculated from the ratio of height and
             weight, within a range of 18.5 to 35.

          -  Willing to be medication and supplement free 2 weeks prior to beginning study, and
             throughout the study. All forms of birth control are okay.

        Exclusion Criteria:

          -  Individuals unwilling or unable to comply with the study protocol (e.g. unable to
             remain medication or supplement free during the study).

          -  Individuals unwilling or unable to take bupropion or have an allergy to bupropion

          -  Any medical or surgical conditions which might significantly alter bupropion
             absorption (e.g., history of malabsorption, liver disease, gastric bypass surgery )

          -  Individuals with a history of psychiatric or neurological illness, including seizure
             disorders

          -  Nicotine dependence

          -  Alcohol dependence

          -  Pregnant or nursing women