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Plasma was collected at pre\u2010specified timepoints over 24\u00a0hours, and the samples were analyzed using liquid chromatography\u2013mass spectrometry for APAP, APAPglucuronide (APAP\u2010gluc), APAP\u2010sulfate (APAP\u2010sulf), APAP\u2010cysteine (APAP\u2010cys), and APAP\u2010Nacetylcysteine (APAP\u2010nac).<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Following RYGBS, peak APAP concentrations at the 3\u2010month and 12\u2010month visits increased by 2.0\u2010fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP\u2010gluc, APAP\u2010sulf, APAP\u2010cys, and APAP\u2010nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)\u2010to\u2010APAP AUC for all four metabolites decreased at 3 and 12\u00a0months post\u2010RYGBS compared to the presurgical baseline. In a simulation of expected steady\u2010state plasma concentrations following multiple dosing of 650\u00a0mg APAP every 4 hours, post\u2010RYGBS patients had higher steady\u2010state peak APAP concentrations compared to healthy individuals and obese pre\u2010RYGBS patients, though APAP exposure was unchanged compared to healthy individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2368","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T06:44:46Z","timestamp":1579589086000},"page":"191-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Impact of Proximal Roux\u2010en\u2010Y Gastric Bypass Surgery on 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