Bupropion’s Bioinequivalence: Patient Variability, Absorption, and Metabolism.

[摘要] Bupropion is a clinically available drug product, marketed as Wellbutrin and Zyban.Bupropion is a norepinephrine/dopamine reuptake inhibitor used for major depressive disorder, seasonal affective disorder, and smoking cessation.A single dose bioequivalence (BE) study was performed for generic versions of bupropion and the name brand product, Wellbutrin.Due to dose related seizures associated with the 300 mg dose, BE studies with the 150 mg dose was extrapolated to the 300 mg dose.However, after complaints of lack of efficacy and adverse effects, the FDA conducted a pilot study on one generic (Budeprion 300 XL) with Wellbutrin 300 XL where it was found that some of the 300 mg generic formulations were bioinequivalent.Therefore, the purpose of these studies was to understand how absorption, metabolism/ metabolic enzymes expression, and patient variability influenced bupropion’s pharmacokinetics.Bupropion produced three active metabolites via two separate pathways, cytochrome P450 2B6 and carbonyl reductase.We compared the relative contribution of the two metabolic pathways of bupropion (by cytochrome P450 2B6 and carbonyl reductase) in the subcellular fractions of liver and intestine, investigated the difference of bupropion’s metabolism in both liver and intestines, and identified which carbonyl reductases might be responsible for bupropion’s metabolism.Secondly, we looked at healthy individuals to see how differences in both enzyme expression (such as polymorphisms in cytochrome P450 2B6) and various formulations (immediate, sustained, or extended release) can affect the pharmacokinetics of bupropion and metabolites in humans.

[发布机构] University of Michigan

[效力级别] Bioinequivalence

[关键词] Bupropion;Bioinequivalence;Science (General);Science;Pharmaceutical Sciences