Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns

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

Timeline

Start

2014-04

Primary completion

2016-11

Completion

2016-11

Drugs

Indications