Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns

Overview

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: November 2016

Interventions

  • Drug: generic bupropion
    • 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.

Arms, Groups and Cohorts

  • Active Comparator: generic bupropion IR75
    • One oral dose of generic bupropion IR75
  • Active Comparator: generic bupropion IR100
    • One oral dose of generic bupropion IR100
  • Active Comparator: generic bupropion SR100
    • One oral dose of generic bupropion SR100
  • Active Comparator: generic bupropion SR150
    • One oral dose of generic bupropion SR150
  • Active Comparator: generic bupropion XL150
    • One oral dose of generic bupropion XL150
  • Active Comparator: generic bupropion XL300
    • One oral dose of generic bupropion XL300

Clinical Trial Outcome Measures

Primary Measures

  • Comparision of the Buproprion Area Under the Concentration Time Curve (AUC) From Time 0 to 96 Hours by Type of Formulation and Dosage
    • Time Frame: 4 days
    • Each formulation of buproprion has a different rate of release. Some release the drug immediately while others release the drug slowly. We will compare the exposure of buproprion by formulation and dose by looking at the area under the concentration time curve. The area under the concentration time curve is a mathematical way of looking at drug exposure in the body. The reported values are AUC (0-96 hours).

Secondary Measures

  • Comparision of the Buproprion Maximum Concentration (Cmax) by Type of Formulation and Dosage
    • Time Frame: 4 days
    • Each formulation of buproprion has a different rate of release. Some release the drug immediately while others release the drug slowly. We will compare the exposure of buproprion by formulation and dose by looking at the maximum concentration. The maximum concentration depends on the rate of drug release and so looking at this value can help us compare differences between formulation.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 25 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Michigan
  • Provider of Information About this Clinical Study
    • Principal Investigator: Duxin Sun, Professor of Pharmaceutical Sciences – University of Michigan
  • Overall Official(s)
    • Duxin Sun, PhD, Principal Investigator, University of Michigan

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