Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns
This trial is active, not recruiting.
|Sponsor||University of Michigan|
|Start date||April 2014|
|End date||November 2016|
|Trial size||50 participants|
|Trial identifier||NCT02078180, HHSF223201310164C, HUM00081894|
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
|Intervention model||crossover assignment|
|Masking||single blind (outcomes assessor)|
|Primary purpose||basic science|
PK parameters for bupropion formulations: half-life (t1/2), volume of distribution (Vd/F), oral clearance (CL/F), maximum drug concentration (Cmax), time to reach Cmax (Tmax), area under the concentration vs. time curve (AUC), absorption rate constant
time frame: Pharmacokinetic (PK) data will be collected over time points: 0, 0.5, 1, 2, 3, 4, 6, 8, 12*, 24, 48, 72, and 96 hours post-dose. *XL formulation only.
Male or female participants from 25 years up to 55 years old.
- 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.
- 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
|Official title||Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns|
|Principal investigator||Duxin Sun, PhD|
Call for more information