Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns

Study Overview
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Brief Summary
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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

Official Title
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Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns

Conditions
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Depression

Intervention / Treatment
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* Drug: generic bupropion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: generic bupropion IR75<br>One oral dose of generic bupropion IR75 | Drug: generic bupropion<br>* 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.<br>* Other names: Wellbutrin;|
| Active Comparator: generic bupropion IR100<br>One oral dose of generic bupropion IR100 | Drug: generic bupropion<br>* 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.<br>* Other names: Wellbutrin;|
| Active Comparator: generic bupropion SR100<br>One oral dose of generic bupropion SR100 | Drug: generic bupropion<br>* 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.<br>* Other names: Wellbutrin;|
| Active Comparator: generic bupropion SR150<br>One oral dose of generic bupropion SR150 | Drug: generic bupropion<br>* 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.<br>* Other names: Wellbutrin;|
| Active Comparator: generic bupropion XL150<br>One oral dose of generic bupropion XL150 | Drug: generic bupropion<br>* 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.<br>* Other names: Wellbutrin;|
| Active Comparator: generic bupropion XL300<br>One oral dose of generic bupropion XL300 | Drug: generic bupropion<br>* 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.<br>* Other names: Wellbutrin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparision of the Buproprion Area Under the Concentration Time Curve (AUC) From Time 0 to 96 Hours by Type of Formulation and Dosage | 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). | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparision of the Buproprion Maximum Concentration (Cmax) by Type of Formulation and Dosage | 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. | 4 days |