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Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic\u2013pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed\u2010effect modeling approach. A parent\u2013metabolite model with first\u2010order absorption, 2\u2010compartments for SV and 1\u2010compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL\u2010cholesterol production. 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In conclusion, individuals post\u2010RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non\u2010statin drugs to attain equivalent responses and mitigate potential adverse events.<\/jats:p>","DOI":"10.1002\/jcph.6110","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T11:44:17Z","timestamp":1722858257000},"page":"1473-1483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Redefining Statin Dosage Post\u2010Gastric Bypass: Insights from a Population Pharmacokinetics\u2013Pharmacodynamics Link Approach"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-0699","authenticated-orcid":false,"given":"Ana Carolina","family":"Conchon Costa","sequence":"first","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Ivan Marques","family":"Medeiros","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences S\u00e3o Paulo State University (UNESP)  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonho","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila A.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy University of Florida  Orlando Florida USA"},{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane M.","family":"de Gaitani","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo (USP)  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayrla E. 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