{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:52:15Z","timestamp":1789501935981,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Bupropion is metabolized to its active metabolite, hydroxybupropion (HB), by the genetically polymorphic cytochrome P450 2B6 (CYP2B6) enzyme. Despite its significant role in bupropion metabolism, the magnitude of the impact of\n                      <jats:italic>CYP2B6<\/jats:italic>\n                      \u00a0genotype on the exposure of bupropion has not been quantified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      A systematic review and meta\u2010analysis was conducted to quantify the association of bupropion and HB exposure with\n                      <jats:italic>CYP2B6<\/jats:italic>\n                      variant alleles and genotype\u2010defined metabolizer phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MEDLINE, EMBASE, Web of Science, Scifinder, PsycINFO, and CENTRAL were screened to identify studies that met the following inclusion criteria (search updated on February 2021): (1) area under the plasma drug concentration\u2010time curve (AUC) of bupropion and\/or HB in relation to\n                      <jats:italic>CYP2B6<\/jats:italic>\n                      \u00a0genotypes was studied, and (2) study participants were genotyped for common\n                      <jats:italic>CYP2B6<\/jats:italic>\n                      variant alleles including at least\n                      <jats:italic>CYP2B6*6<\/jats:italic>\n                      . The Newcastle Ottawa Scale was used to assess risk of bias in each included study. The ratio of means (RoM) between\n                      <jats:italic>CYP2B6<\/jats:italic>\n                      \u00a0genotype or genotype\u2010defined phenotype groups for bupropion exposure was calculated for each study and combined in a meta\u2010analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven studies met the inclusion criteria for this systematic review, and 10 (including N\u00a0=\u00a0413 participants) were included in the meta\u2010analysis. All 10\u00a0studies involved healthy adult volunteers, where other medications were not allowed. The AUCs of HB and the active moiety (bupropion + HB) were significantly reduced in\n                      <jats:italic>CYP2B6*6<\/jats:italic>\n                      carriers compared with the non\u2010carriers (HB: RoM 0.77, 95% CI 0.71\u20130.83; active moiety: RoM 0.81, 95% CI 0.75\u20130.88). Both CYP2B6 poor and intermediate metabolizers had significantly decreased exposures to HB and the active moiety than normal metabolizers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>CYP2B6*6<\/jats:italic>\n                      allele and genotype\u2010determined CYP2B6 poor and intermediate metabolizer phenotypes are associated with significantly lower exposures to HB and the total active moiety. The findings of this study suggest opportunities to further study precision dosing strategies for bupropion therapy based on\n                      <jats:italic>CYP2B6<\/jats:italic>\n                      \u00a0genotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.2644","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T13:03:22Z","timestamp":1636463002000},"page":"34-44","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Association of\n                    <i>CYP2B6<\/i>\n                    genetic polymorphisms with bupropion and hydroxybupropion exposure: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-7447","authenticated-orcid":false,"given":"Seenae","family":"Eum","sequence":"first","affiliation":[{"name":"Department of Pharmacogenomics School of Pharmacy Shenandoah University Fairfax Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin","family":"Sayre","sequence":"additional","affiliation":[{"name":"Librarian Department Thompson Rivers University Kamloops British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Stingl","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology University Hospital of RWTH Aachen Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Bishop","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"},{"name":"Department of Psychiatry and Behavioral Sciences Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Practice Guideline for the Treatment of Patients with Major Depressive Disorder","author":"American Psychiatric Association","year":"2010"},{"key":"e_1_2_7_3_1","unstructured":"The Management of Major Depressive Disorder Working Group Management.VA\/DoD clinical practice guideline for the management of major depressive disorder.2016."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.10.027"},{"key":"e_1_2_7_5_1","unstructured":"Agency for Healthcare Research and Quality (AHRQ) Rockville. 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