Titre du document / Document title

Bupropion for major depressive disorder : Pharmacokinetic and formulation considerations

Auteur(s) / Author(s)

JEFFERSON James W. ⁽¹⁾ ; PRADKO James F. ⁽²⁾ ; MUIR Keith T. ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Madison Institute of Medicine and Department of Psychiatry, University of Wisconsin Medical School, Madison, Wisconsin, ETATS-UNIS
⁽²⁾ Bay Pointe Medical Center, New Baltimore, Michigan, and Mount Clemens General Hospital and St. John Hospital, Detroit, Michigan, ETATS-UNIS
⁽³⁾ Division of Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, ETATS-UNIS

Résumé / Abstract

Background: 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. Objectives: 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. Methods: 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 pharmaco-kinetics, 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. Results: 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 should be considered. In addition, bupropion inhibits CYP2D6 and may reduce clearance of agents metabolized by this enzyme. Absorption of the XL formulation is prolonged compared with the IR and SR formulations (T_max, -5 hours vs ∼1.5 and -3 hours, respectively). Bupropion is dosed without regard to food. Conclusions: Understanding the PK profile and formulations of bupropion can help optimize clinical use. Bupropion is metabolized extensively, resulting in 3 active metabolites. This metabolic profile, various patient factors (eg, age, medical illnesses), and potential drug interactions should be considered when prescribing bupropion. The 3 formulations-bupropion, bupropion SR, and bupropion XL-are bioequivalent and offer options to optimize treatment for patients with MDD.

Revue / Journal Title

Clinical therapeutics   ISSN 0149-2918 

Source / Source

2005, vol. 27, n^o11, pp. 1685-1695 [11 page(s) (article)] (66 ref.)

Langue / Language

Anglais

Editeur / Publisher

Excerpta Medica, Belle Mead, NJ, ETATS-UNIS  (1977) (Revue)

Mots-clés anglais / English Keywords

Mood disorder ; Antidepressant agent ; Psychotropic ; Drug interaction ; Depressions ; Formulation ; Pharmacokinetics ; Depression ; Bupropion ;

Mots-clés français / French Keywords

Trouble humeur ; Antidépresseur ; Psychotrope ; Interaction médicamenteuse ; Dépression ; Formulation ; Pharmacocinétique ; Etat dépressif ; Bupropione ;

Mots-clés espagnols / Spanish Keywords

Trastorno humor ; Antidepresor ; Psicotropo ; Interacción medicamentosa ; Depresión ; Formulación ; Farmacocinética ; Estado depresivo ; Bupropión ;

Mots-clés d'auteur / Author Keywords

bupropion ; depression ; major depressive disorder ; pharmacokinetics ; formulations ; drug interactions ;

Localisation / Location

INIST-CNRS, Cote INIST : 18353, 35400013440806.0020