title: Identification and Structural Characterization of Three New Metabolites of Bupropion in Humans.
abstract: Bupropion is a widely used antidepressant and the recommended CYP2B6 probe drug. However, current understanding of bupropion elimination pathways is limited. Bupropion has three active circulating metabolites, OH-bupropion, threohydrobupropion, and erythrohydrobupropion, but together with bupropion these metabolites and their conjugates in urine represent only 23% of the dose, and the majority of the elimination pathways of bupropion result in uncharacterized metabolites. The aim of this study was to determine the structures of the uncharacterized bupropion metabolites using human clinical samples and in vitro incubations. Three new metabolites, 4'-OH-bupropion, erythro-4'-OH-hydrobupropion, and threo-4'-OH-hydrobupropion, were detected in human liver microsome incubations and were isolated from human urine. The structures of the metabolites were confirmed via comparison of UV absorbance, NMR spectra, and mass spectral data to those of the synthesized standards. In total, these metabolites represented 24% of the drug related material excreted in urine.
authors.affiliation: Departments of Pharmaceutics, Obstetrics and Gynecology, and Medicinal Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Sager
authors.affiliation: Departments of Pharmaceutics, Obstetrics and Gynecology, and Medicinal Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Choiniere
authors.affiliation: Departments of Pharmaceutics, Obstetrics and Gynecology, and Medicinal Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Justine
authors.initials: J
authors.lastname: Chang
authors.affiliation: Departments of Pharmaceutics, Obstetrics and Gynecology, and Medicinal Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Stephenson-Famy
authors.affiliation: Departments of Pharmaceutics, Obstetrics and Gynecology, and Medicinal Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Wendel L
authors.initials: WL
authors.lastname: Nelson
authors.affiliation: Departments of Pharmaceutics, Obstetrics and Gynecology, and Medicinal Chemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Nina
authors.initials: N
authors.lastname: Isoherranen
keywords: Bupropion; aromatic hydroxylation; metabolites; structural characterization