{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:45:20Z","timestamp":1791686720592,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Abstract<\/jats:title>Sertraline is a selective serotonin reuptake inhibitor widely metabolized in the liver by cytochrome P450 (CYP<\/jats:styled-content>) enzymes. Besides, it is a P\u2010glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of this study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty\u2010six healthy volunteers (24 men and 22 women) receiving a 100\u2010mg single oral dose of sertraline were genotyped for 17 genetic variants ofCYP<\/jats:styled-content>enzymes (CYP<\/jats:styled-content>2B6<\/jats:italic>,CYP<\/jats:styled-content>2C9<\/jats:italic>,CYP<\/jats:styled-content>2C19<\/jats:italic>,CYP<\/jats:styled-content>2D6<\/jats:italic>),<\/jats:italic>ATP<\/jats:styled-content>\u2010binding cassette subfamily B member 1 (ABCB<\/jats:styled-content>1<\/jats:italic>), solute carrier family 6 member 4 (SLC<\/jats:styled-content>6A4<\/jats:italic>), 5\u2010hydroxytryptamine receptor 2A (HTR<\/jats:styled-content>2A<\/jats:italic>) and 5\u2010hydroxytryptamine receptor 2C (HTR<\/jats:styled-content>2C<\/jats:italic>) genes. Pharmacokinetic and pharmacodynamic parameters were similar in men and women. Polymorphisms inCYP<\/jats:styled-content>2C19<\/jats:italic>andCYP<\/jats:styled-content>2B6<\/jats:italic>genes influenced sertraline pharmacokinetics, with a greater effect ofCYP<\/jats:styled-content>2C19<\/jats:italic>. Individuals carrying defective alleles forCYP<\/jats:styled-content>2C19<\/jats:italic>andCYP<\/jats:styled-content>2B6<\/jats:italic>showed higher area under the curve (AUC<\/jats:styled-content>) and half\u2010life (T<\/jats:italic>1\/2<\/jats:sub>). Moreover,CYP<\/jats:styled-content>2C19*17<\/jats:italic>was related to a decreasedAUC<\/jats:styled-content>andT<\/jats:italic>1\/2<\/jats:sub>. No significant effect was found for polymorphisms inCYP<\/jats:styled-content>2C9<\/jats:italic>,CYP<\/jats:styled-content>2D6<\/jats:italic>andABCB<\/jats:styled-content>1<\/jats:italic>on sertraline pharmacokinetics. Sertraline had a small heart rate\u2010lowering effect, directly related to maximum concentration (C<\/jats:italic>max<\/jats:sub>) and the presence ofABCB<\/jats:styled-content>1<\/jats:italic>minor alleles. Sertraline had no significant effect on blood pressure andQT<\/jats:styled-content>c. There was a tendency to present more adverse drug reactions in women and individuals with higherAUC<\/jats:styled-content>of sertraline, such asCYP<\/jats:styled-content>2C19<\/jats:italic>intermediate metabolizers andCYP<\/jats:styled-content>2B6<\/jats:italic>G516T T\/T individuals.<\/jats:p>","DOI":"10.1111\/bcpt.12938","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T17:12:43Z","timestamp":1510679563000},"page":"501-511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Effect of Polymorphisms on the Pharmacokinetics, Pharmacodynamics and Safety of Sertraline in Healthy Volunteers"],"prefix":"10.1111","volume":"122","author":[{"given":"Miriam","family":"Saiz\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de la Princesa Instituto Te\u00f3filo Hernando Instituto de Investigaci\u00f3n Sanitaria la 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Hospital Universitario de la Princesa Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/354066a0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1017\/S1461145711000551","article-title":"Efficacy of antidepressants: similar but different","volume":"14","author":"Matthews PR","year":"2011","journal-title":"Int J Neuropsychopharmacol"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707253"},{"key":"e_1_2_10_5_1","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios (AEMPS) label information for sertraline.https:\/\/www.aemps.gob.es\/cima\/fichasTecnicas.do?metodo=buscar(last accessed 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