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The study aimed to evaluate PGx, demographic, clinical, and prescribing determinants of sertraline plasma concentrations, sertraline plasma concentration-to-dose ratio (C\/D), and non-dose-normalized sertraline-to-norsertraline metabolic ratio (MR), with log10-transformed dose-normalized sertraline\/norsertraline metabolic ratio (LogMRDN) and log10-transformed MR (LogMR) evaluated as exploratory derived pharmacokinetic outcomes in real-world clinical settings. Methods: This prospective real-world PGx study included 153 patients receiving sertraline therapy who participated in the MedeA clinical PGx implementation program. Associations of genotype-predicted phenotypes for CYP2C19, CYP2B6, CYP2D6, CYP2C9, and CYP3A4, CYP2C:TG haplotype status, demographic, clinical, and prescribing characteristics with sertraline concentration, C\/D, MR, and LogMRDN were evaluated using univariable analyses. Separate multivariable linear regression models were fitted for these outcomes and LogMR using 140 complete cases. Results: CYP2C19 gPM status was associated with higher sertraline concentrations (\u03b2 = 72.10, 95% CI: 21.36\u2013122.84; p = 0.01). Although a higher sertraline C\/D ratio was observed in the conventional multivariable model with CYP2C19 gPM (\u03b2 = 1.46, 95% CI: 0.85\u20132.08; p &lt; 0.001), this association was not retained after HC3 heteroscedasticity-robust standard errors were applied (\u03b2 = 1.46, 95% CI: \u22120.09\u20133.02; p = 0.07). In a small exploratory subgroup analysis, patients with combined CYP2C19 and CYP2B6 poor-metabolizer status (n = 2) had sertraline concentrations exceeding 150 ng\/mL. Conclusions: The study findings provide further insights into the relevance of CYP2C19 in sertraline pharmacokinetics.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091133","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:24:02Z","timestamp":1788945842000},"page":"1133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenetic, Clinical, Prescribing, and Demographic Predictors of Sertraline Pharmacokinetics"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6787-7025","authenticated-orcid":false,"given":"Carla Gonz\u00e1lez","family":"de la Cruz","sequence":"first","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levin","family":"Thomas","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1849-1093","authenticated-orcid":false,"given":"Carmen","family":"Mata-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"},{"name":"Clinical Pharmacology Service, Pharmacogenomics and Personalized Medicine Unit, Badajoz University Hospital, Extremadura Health Service (SES), 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-7784","authenticated-orcid":false,"given":"Juan Antonio","family":"Villatoro-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1076-0743","authenticated-orcid":false,"given":"Fernando","family":"de Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Food Technology, Faculty of Pharmacy, University of Castilla-La Mancha, 02008\u00a0Albacete, Spain"},{"name":"Regional Institute of Applied Scientific Research IRICA, University of Castilla-La Mancha, 13004 Ciudad Real, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8517-4802","authenticated-orcid":false,"given":"Idian","family":"Gonz\u00e1lez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"},{"name":"Psychiatry Unit, San Pedro de Alc\u00e1ntara Hospital, Extremadura Health Service (SES), 10002 C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idilio","family":"Gonz\u00e1lez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"},{"name":"Psychiatry Unit, Llerena Hospital, Extremadura Health Service (SES), 06900 Llerena, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Pe\u00f1as-Lled\u00f3","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5663-7081","authenticated-orcid":false,"given":"Adri\u00e1n","family":"LLerena","sequence":"additional","affiliation":[{"name":"Personalised Medicine and Mental Health Unit, University Institute for Biosanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain"},{"name":"Clinical Pharmacology Service, Pharmacogenomics and Personalized Medicine Unit, Badajoz University Hospital, Extremadura Health Service (SES), 06006 Badajoz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1208\/s12248-020-00455-y","article-title":"Population pharmacokinetics of sertraline in healthy subjects: A model-based meta-analysis","volume":"22","author":"Alhadab","year":"2020","journal-title":"AAPS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.2165\/00003088-200241150-00002","article-title":"Clinical pharmacokinetics of sertraline","volume":"41","author":"DeVane","year":"2002","journal-title":"Clin. 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