Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations

• Published in: Clinical therapeutics 2005-11, Vol.27 (11), p.1685-1695
• Main Authors: Jefferson, James W., Pradko, James F., Muir, Keith T.
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Animals; Antidepressants; Antidepressive Agents, Second-Generation - administration & dosage; Antidepressive Agents, Second-Generation - pharmacokinetics; Antidepressive Agents, Second-Generation - therapeutic use; Area Under Curve; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Bupropion - administration & dosage; Bupropion - pharmacokinetics; Bupropion - therapeutic use; Comorbidity; Cytochrome; Cytochrome P-450 CYP2B6; Delayed-Action Preparations; Depressive Disorder, Major - complications; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Dopamine; Drug dosages; Drug Interactions; Drug therapy; Half-Life; Humans; Liver Failure - complications; Liver Failure - metabolism; Medical sciences; Mental depression; Metabolic Clearance Rate; Metabolism; Oxidoreductases, N-Demethylating - genetics; Pharmacokinetics; Pharmacology. Drug treatments; Physicians; Polymorphism, Genetic; Psychiatry; Renal Insufficiency - complications; Renal Insufficiency - metabolism; Sex Factors; Sexual disorders; Smoking - metabolism; Smoking cessation; Surveillance
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2005.11.011

Major depressive disorder (MDD) is a common psychiatric condition, with 6.6% of the adult population in the United States experiencing a major depressive episode during any given year. Depressed patients must receive adequate treatment to maximize the likelihood of clinical success. Bupropion hydrochloride, a noradrenergic/dopaminergic antidepressant, is available in 3 oral formulations: immediate release (IR) (given TID), sustained release (SR) (given BID), and extended release (XL) (given QD). Understanding the pharmacokinetic (PK) properties and formulations of bupropion can help optimize clinical use. The aims of this article were to provide a review of the PK properties of bupropion and identify its various formulations and clinical applications to help optimize treatment of MDD. In this review, data concerning PK trials/reports were collected from articles identified using a PubMed search. The search was conducted without date limitations and using the search terms bupropion, bupropion SR, bupropion XL, bupropion pbarmacokinetics, bupropion metabolism, and bupropion drug interactions. Additional reports were selected from references that appeared in articles identified in the original search. In addition, data from studies summarized in product information and labeling were obtained. All available information, concentrating on studies in humans, pertinent to bupropion PK properties and/or formulations was included. Bupropion is extensively metabolized by the liver (t 1/2, ∼21 hours). Hydroxybupropion, the primary active metabolite (t 1/2, ∼20 hours), is formed by cytochrome P450 (CYP) 2B6. At steady state, C max of hydroxybupropion is 4- to 7-fold higher, and the AUC is ∼10-fold greater, compared with those of the parent drug. Threohydrobupropion and erythrohydrobupropion (mean [SD] t 1/2 values, ∼37 [13] and ∼33 [10] hours, respectively), the other active metabolites of bupropion, are formed via nonmicrosomal pathways. Relative to bupropion, the C max values are ∼5-fold greater for threohydrobupropion and similar for erythrohy-drobupropion. Based on a mouse antitetrabenazine model, hydroxybupropion is ∼50% as active as bupropion, and threohydrobupropion and erythrohy-drobupropion are ∼20% as active as bupropion. Bupropion lowers the seizure threshold and, therefore, concurrent administration with other agents that lower the seizure threshold should be undertaken cautiously. Potential interactions with other agents that are metabolized by CYP2B6 shou