{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:06:24Z","timestamp":1772600784587,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Roux\u2010en\u2010Y gastric bypass is one of the most common surgical treatments for obesity due to the effective long\u2010term weight loss and remission of associated comorbidities. Carvedilol, a third\u2010generation \u03b2\u2010blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH\u2010dependent solubility and dissolution and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after roux\u2010en\u2010Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux\u2010en\u2010Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n\u00a0=\u00a015, body mass index\u00a0&lt;\u00a025\u00a0kg\/m<jats:sup>2<\/jats:sup>), obese (n\u00a0=\u00a019, body mass index\u00a0\u2265\u00a030), and post\u2010roux\u2010en\u2010Y gastric bypass subjects submitted to surgery for at least 6\u00a0months (n\u00a0=\u00a019) were investigated. All subjects were administered a single oral dose of 25\u2010mg racemic carvedilol, and blood was sampled for up to 24\u00a0hours. Plasma concentrations of (<jats:italic>R<\/jats:italic>)\u2010 and (<jats:italic>S<\/jats:italic>)\u2010carvedilol were determined by liquid chromatography\u2013tandem mass spectrometry. The maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and the area under the plasma concentration\u2010time curve (AUC) of (<jats:italic>R<\/jats:italic>)\u2010carvedilol were 2\u2010 to 3\u2010fold higher than (<jats:italic>S<\/jats:italic>)\u2010carvedilol in all groups. Obese subjects have shown reduced C<jats:sub>max<\/jats:sub> of (<jats:italic>R<\/jats:italic>)\u2010 and (<jats:italic>S<\/jats:italic>)\u2010carvedilol without changing the AUC. Post\u2010roux\u2010en\u2010Y gastric bypass subjects presented a 3.5\u2010fold reduction in the C<jats:sub>max<\/jats:sub> of the active (<jats:italic>S<\/jats:italic>)\u2010carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach C<jats:sub>max<\/jats:sub> of (<jats:italic>S<\/jats:italic>)\u2010carvedilol increased 2.5\u2010fold in post\u2010roux\u2010en\u2010Y gastric bypass subjects compared to obese or nonobese. Although the \u03b2\u2010blockade response was not assessed, the reduced exposure to carvedilol in subjects post\u2010roux\u2010en\u2010Y gastric bypass may be clinically relevant and require dose adjustment.<\/jats:p>","DOI":"10.1002\/jcph.2221","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T04:23:45Z","timestamp":1677644625000},"page":"838-847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Roux\u2010En\u2010Y Gastric Bypass in the Pharmacokinetics of (<i>R<\/i>)\u2010Carvedilol and (<i>S<\/i>)\u2010Carvedilol"],"prefix":"10.1002","volume":"63","author":[{"given":"Priscila Akemi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"},{"name":"Center for Pharmacometrics and Systems Pharmacology College of Pharmacy University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Cristofoletti","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology College of Pharmacy University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valvanera","family":"Vozmediano","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology College of Pharmacy University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane Masetto","family":"de Gaitani","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo Moreira","family":"da Silva","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Kemp","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajith Kumar","family":"Sankarankutty","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson","family":"Salgado Junior","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Sebasti\u00e3o dos","family":"Santos","sequence":"additional","affiliation":[{"name":"School of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia Valadares","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology College of Pharmacy University of Florida  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"American Society for Metabolic and Bariatric Surgery (ASMBS).Estimate of Bariatric Surgery Numbers 2011\u20132020;2022.https:\/\/www.asmbs.org\/resources\/estimate\u2010of\u2010bariatric\u2010surgery\u2010numbers. Accessed September 13 2022."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0563"},{"key":"e_1_2_11_4_1","volume-title":"StatPearls [Internet]","author":"Mitchell BG","year":"2022"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1Q414"},{"key":"e_1_2_11_6_1","unstructured":"GlaxoSmithKline (GSK).COREG (carvedilol).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/020297s038lbl.pdf. Published September 2017. Accessed September 14 2022."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.34"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007990903533681"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-015-0365-2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01409476"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199219001-00028"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.30.1930"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.10.004"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.24505"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(96)00092-8"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2016.08.007"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.30.2146"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.31.1297"},{"key":"e_1_2_11_19_1","unstructured":"Centers for Disease Control and Prevention.Defining Adult Overweight & Obesity.https:\/\/www.cdc.gov\/obesity\/basics\/adult\u2010defining.html. Accessed November 12 2022."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2022.123338"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2102953"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248410372926"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12109"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1985.tb05112.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-9236(95)90036-5"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2021.07.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-008-9055-7"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12030295"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp100630"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-021-05308-x"},{"issue":"12","key":"e_1_2_11_31_1","first-page":"784","article-title":"The effects of surfactants on the solubility and dissolution profiles of a poorly water\u2010soluble basic drug, carvedilol","volume":"70","author":"Incecayir T","year":"2015","journal-title":"Pharmazie"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.311"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.46.120604.141059"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200039030-00004"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.2165\/11599410-000000000-00000"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1999.00709.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-020-02421-y"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15349"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2210-9-S2-A38"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-57002-9"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1990.tb03668.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1994.tb02857.x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2006.00408.x"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1810"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1560"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.0c00559"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.30.537"},{"key":"e_1_2_11_48_1","unstructured":"OeserSG.The Effect of Obesity on UGT Enzyme Expression Activity and Modeled Hepatic Clearance by Glucuronidation. Thesis. University of Hawaii at Manoa.2013.https:\/\/scholarspace.manoa.hawaii.edu\/server\/api\/core\/bitstreams\/37c22e01\u2010d182\u201043e9\u20109bb2\u2010f883bdaf1fd3\/content. Accessed January 24 2023"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.07.016"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.07.015"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00464-012-2716-3"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800691108"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12087"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2017.07.031"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2221","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.2221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T19:17:33Z","timestamp":1692472653000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.2221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,6]]},"references-count":53,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/jcph.2221"],"URL":"https:\/\/doi.org\/10.1002\/jcph.2221","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,6]]},"assertion":[{"value":"2022-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}