{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T03:57:28Z","timestamp":1782359848204,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>The antidepressant bupropion is stereoselectively metabolized and metabolite enantiomers have differential pharmacologic effects, but steady\u2010state enantiomeric disposition is unknown. Controversy persists about bupropion XL 300\u00a0mg generic equivalence to brand product, and whether generics might have different stereoselective disposition leading to enantiomeric non\u2010bioequivalence and, thus, clinical nonequivalence. This preplanned follow\u2010on analysis of a prospective, randomized, double\u2010blinded, crossover study of brand and 3 generic bupropion XL 300\u00a0mg products measured steady\u2010state enantiomeric plasma and urine parent bupropion and primary and secondary metabolite concentrations and evaluated bioequivalence and pharmacokinetics. Steady\u2010state plasma and urine bupropion disposition was markedly stereoselective, with up to 40\u2010fold differences in plasma concentrations of the active metabolite <jats:italic>S<\/jats:italic>,<jats:italic>S<\/jats:italic>\u2010hydroxybupropion vs. <jats:italic>R<\/jats:italic>,<jats:italic>R<\/jats:italic>,\u2010hydroxybupropion. Urine metabolite glucuronides were prominent, but glucuronidation was metabolite\u2010specific and enantioselective. There were no differences between any generic and brand, or between generics, in plasma enantiomer concentrations of bupropion or the major metabolites. All generic products satisfied formal bioequivalence criteria (peak plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the plasma concentration\u2010time curve over 24\u00a0hours (AUC<jats:sub>0\u201324<\/jats:sub>)) using enantiomers for bupropion as well as for metabolites, and generics were comparable to each other, and were considered bioequivalent, based on enantiomeric analysis. Enantiomeric bioequivalence explains the previously observed therapeutic equivalence of bupropion generics and brand in treating major depression. These results have important implications for understanding the clinical therapeutic effects of bupropion based on complex and stereoselective metabolism.<\/jats:p>","DOI":"10.1002\/cpt.1888","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T10:40:20Z","timestamp":1589020820000},"page":"1036-1048","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Stereoselective Steady\u2010State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults"],"prefix":"10.1111","volume":"108","author":[{"given":"Evan D.","family":"Kharasch","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Duke University School of Medicine Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Neiner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Kraus","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Blood","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Philip","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Lenze","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045125316629071"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.151510"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881117737401"},{"key":"e_1_2_10_4_1","first-page":"CD009504","article-title":"Bupropion for attention deficit hyperactivity disorder (ADHD) in adults","volume":"10","author":"Verbeeck W.","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2018.1501359"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2018.06.038"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-019-05074-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-019-0803-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200262002-00002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.10.005"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.186"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000042"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-3908-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.068932"},{"key":"e_1_2_10_15_1","unstructured":"GlaxoSmithKline (GSK) reviews novel therapeutics for CNS disorders and confirms strong pipeline momentum (Press Release 11\/23\/2004)<https:\/\/web.archive.org\/web\/20070928041150\/http:\/\/www.biospace.com\/news_story.aspx?StoryID=18222420&full=1> (2004). Accessed August 27 2018."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-008-9535-1"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.072363"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.068908"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2007.07.007"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008314254"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.232876"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.05.036"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.02.032"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1116"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01600-07"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)02010-7"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.001313"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.166850"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm1003232"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.6b00189"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2046"},{"key":"e_1_2_10_32_1","unstructured":"Review of therapeutic equivalence generic Bupropion XL 300 mg and Wellbutrin XL 300 mg. US Food and Drug Administration (FDA) archived at: <https:\/\/www.fda.gov\/AboutFDA\/CentersOffices\/OfficeofMedicalProductsandTobacco\/CDER\/ucm153270.htmhttps:\/\/wayback.archive\u2010it.org\/7993\/20171102213516\/> (2012)."},{"key":"e_1_2_10_33_1","unstructured":"Update: Budeprion XL 300 mg not therapeutically equivalent to Wellbutrin XL 300 mg. Food and Drug Administration (FDA) Center for Drug Evaluation and Research <http:\/\/www.fda.gov\/Drugs\/DrugSafety\/PostmarketDrugSafetyInformationforPatientsandProviders\/ucm322161> (2012)."},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1212969"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1309"},{"key":"e_1_2_10_36_1","unstructured":"US Food and Drug Administration Center for Drug Evaluation and Research.Guidance for industry: Statistical approaches to establishing bioequivalence<https:\/\/www.fda.gov\/downloads\/Drugs\/Guidances\/ucm070244.pdf> (2001)."},{"key":"e_1_2_10_37_1","unstructured":"Food and Drug Administration Center for Drug Evaluation and Research U.S. Department of Health and Human Services.Guidance for industry: Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA<https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm377465.pdf> (2013)."},{"key":"e_1_2_10_38_1","unstructured":"US Food and Drug Administration Center for Drug Evaluation and Research.Guidance for industry: Bioavailability and bioequivalence studies for orally administered drug products \u2010 General considerations<https:\/\/www.ipqpubs.com\/wp\u2010content\/uploads\/2014\/04\/BABEOld.pdf> (2003)."},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-012-9396-8"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.11.005"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32835d9ab0"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2011.11.022"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.072892"},{"key":"e_1_2_10_44_1","unstructured":"Association for Accessible Medicines.Generic drug and biosimilars access and savings<https:\/\/accessiblemeds.org\/resources\/reports\/2019\u2010access\u2010and\u2010savings\u2010report> (2019). Accessed February 1 2020."},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-016-3612-7"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.1688"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.1720"},{"key":"e_1_2_10_48_1","unstructured":"US Food and Drug Administration Center for Drug Evaluation and Research.Update: Bupropion Hydrochloride extended\u2010release 300 mg bioequivalence studies<https:\/\/www.fda.gov\/drugs\/drugsafety\/postmarketdrugsafetyinformationforpatientsandproviders\/ucm322161.htm> (2013). Accessed August 27 2018."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1888","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1888","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1888","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:29:05Z","timestamp":1699363745000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/cpt.1888"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1888","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,30]]},"assertion":[{"value":"2020-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}