Redefining Statin Dosage Post-Gastric Bypass: Insights from a Population Pharmacokinetics–Pharmacodynamics Link Approach

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Autor(es): dc.contributorUniversity of Florida-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorConchon Costa, Ana Carolina-
Autor(es): dc.creatorMedeiros, Jose Ivan Marques-
Autor(es): dc.creatorKang, Wonho-
Autor(es): dc.creatorYamamoto, Priscila A.-
Autor(es): dc.creatorde Gaitani, Cristiane M.-
Autor(es): dc.creatorVasconcelos, Mayrla E. D.-
Autor(es): dc.creatorDa Silva, Rodrigo Moreira-
Autor(es): dc.creatorKemp, Rafael-
Autor(es): dc.creatorSankarankutty, Ajith K.-
Autor(es): dc.creatorSalgado Jr, Wilson-
Autor(es): dc.creatorSantos, Jose Sebastiao-
Autor(es): dc.creatorSchmidt, Stephan-
Autor(es): dc.creatorDe Moraes, Natalia Valadares-
Data de aceite: dc.date.accessioned2025-08-21T20:16:01Z-
Data de disponibilização: dc.date.available2025-08-21T20:16:01Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1002/jcph.6110-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/299335-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/299335-
Descrição: dc.descriptionRoux-en-Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. 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–pharmacodynamic 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-effect modeling approach. A parent–metabolite model with first-order absorption, 2-compartments for SV and 1-compartment 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-cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low-intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post-RYGB patients to maintain a comparable response to that of non-operated subjects. Moderate-intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non-statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post-RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non-statin drugs to attain equivalent responses and mitigate potential adverse events.-
Descrição: dc.descriptionCenter for Pharmacometrics and Systems Pharmacology College of Pharmacy University of Florida-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo (USP), São Paulo-
Descrição: dc.descriptionSchool of Medicine of Ribeirão Preto University of São Paulo (USP), São Paulo-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo-
Formato: dc.format1473-1483-
Idioma: dc.languageen-
Relação: dc.relationJournal of Clinical Pharmacology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectgastric bypass-
Palavras-chave: dc.subjectOATP1B1 genotype-
Palavras-chave: dc.subjectPopPK-
Palavras-chave: dc.subjectsimvastatin hydroxy acid-
Título: dc.titleRedefining Statin Dosage Post-Gastric Bypass: Insights from a Population Pharmacokinetics–Pharmacodynamics Link Approach-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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