{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:44:03Z","timestamp":1793681043310,"version":"4.5.1"},"reference-count":34,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:00:00Z","timestamp":1550707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008433","name":"consejer\u00eda de educaci\u00f3n, juventud y deporte, comunidad de madrid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008433","id-type":"DOI","asserted-by":"publisher"}]},{"name":"H2020 Marie Sklodowska-Curie Innovative Training Network","award":["721236 grant"],"award-info":[{"award-number":["721236 grant"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Agomelatine is an agonist of the melatoninergic receptors used for the treatment of depression. Our aim was to evaluate the effect of genetic polymorphisms in metabolising enzymes and the P-glycoprotein transporter on agomelatine pharmacokinetics and pharmacodynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Twenty-eight healthy volunteers receiving a single 25 mg oral dose of agomelatine, were genotyped for nine polymorphisms in cytochrome P450 enzymes ( CYP1A2, CYP2C9 and CYP2C19) and adenosine triphosphate-binding cassette subfamily B member 1 ( ABCB1), by real-time polymerase chain reaction . Agomelatine concentrations were measured by high performance liquid chromatography coupled to a tandem mass spectrometry detector.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We calculated a CYP1A2 activity score that was directly correlated with agomelatine pharmacokinetics. Individuals with a decreased enzyme activity (*1C carriers) had a lower clearance and accumulated higher concentrations of agomelatine. In contrast, individuals with a high CYP1A2 inducibility (*1F or *1B carriers) showed an extensive clearance and lower agomelatine concentrations. The apparently marked differences between races were due to the different CYP1A2 genotype distribution. CYP2C9 intermediate\/poor metabolisers showed a higher area under the concentration-time curve and maximum concentration. ABCB1 G2677T\/A polymorphism affected the time to reach maximum concentration, as subjects carrying A\/A+A\/T genotypes showed higher values. No association was found for CYP2C19 phenotype. Agomelatine did not produce any change in blood pressure, heart rate or QT interval.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>CYP1A2 polymorphisms affect agomelatine pharmacokinetics. CYP1A2 phenotype inferred from the genotyping of CYP1A2*1C, *1F and *1B alleles might be a potential predictor of agomelatine exposure. ABCB1 G2677T\/A could affect agomelatine absorption, as subjects with A\/A+A\/T genotypes had lower agomelatine concentration and they take more time to reach the maximum concentration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0269881119827959","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T10:06:51Z","timestamp":1550743611000},"page":"522-531","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":53,"title":["Polymorphisms in\n                    <i>CYP1A2, CYP2C9<\/i>\n                    and\n                    <i>ABCB1<\/i>\n                    affect agomelatine pharmacokinetics"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-3135","authenticated-orcid":false,"given":"Miriam","family":"Saiz-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"},{"name":"UICEC Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Belmonte","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"},{"name":"UICEC Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"},{"name":"UICEC Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Research Network), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-0671","authenticated-orcid":false,"given":"Danilo","family":"Vieira de Lara","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Zubiaur","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-0466","authenticated-orcid":false,"given":"Dora","family":"Koller","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Universidad Aut\u00f3noma de Madrid 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