{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T12:05:47Z","timestamp":1747829147890,"version":"3.40.5"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004593","name":"Universidad Aut\u00f3noma de Madrid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["ICI20\/00131"],"award-info":[{"award-number":["ICI20\/00131"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund Plus","doi-asserted-by":"publisher","award":["FI20\/00090"],"award-info":[{"award-number":["FI20\/00090"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ramipril is an angiotensin\u2010converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e., genes encoding for enzymes like CYPs or UGTs and transporters like ABC or SLC) on ramipril pharmacokinetic variability and adverse drug reaction (ADR) incidence. Twenty\u2010nine healthy volunteers who had participated in a single\u2010dose bioequivalence clinical trial of two formulations of ramipril were recruited. A univariate and multivariate analysis searching for associations between genetic variants and ramipril pharmacokinetics was performed. SLCO1B1 and ABCG2 genotype\u2010informed phenotypes strongly predicted ramipril exposure. Volunteers with the SLCO1B1 decreased function (DF) phenotype presented around 1.7\u2010fold higher dose\/weight\u2010corrected area under the curve (AUC\/DW) than volunteers with the normal function (NF) phenotype (univariate <jats:italic>p<\/jats:italic>\u2010value [<jats:italic>p<\/jats:italic><jats:sub>uv<\/jats:sub>]\u2009&lt;\u00a00.001, multivariate <jats:italic>p<\/jats:italic>\u2010value [<jats:italic>p<\/jats:italic><jats:sub>mv<\/jats:sub>]\u2009&lt;\u00a00.001, \u03b2\u2009=\u00a00.533, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.648). Similarly, volunteers with ABCG2 DF\u2009+\u2009poor function (PF) phenotypes presented around 1.6\u2010fold higher AUC\/DW than those with the NF phenotype (<jats:italic>p<\/jats:italic><jats:sub>uv<\/jats:sub>\u00a0=\u00a00.011, <jats:italic>p<\/jats:italic><jats:sub>mv<\/jats:sub>\u00a0&lt;\u00a00.001, \u03b2\u2009=\u00a00.259, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.648). Our results suggest that SLCO1B1 and ABCG2 are important transporters to ramipril pharmacokinetics, and their genetic variation strongly alters its pharmacokinetics. Further studies are required to confirm these associations and their clinical relevance.<\/jats:p>","DOI":"10.1111\/bcpt.14046","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T09:35:39Z","timestamp":1721122539000},"page":"295-307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SLCO1B1 and ABCG2 genotype\u2010informed phenotypes are related to variation in ramipril exposure"],"prefix":"10.1111","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8059-7349","authenticated-orcid":false,"given":"Houwaida","family":"Abbes","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"},{"name":"Biochemistry Department, LR12SP11 Sahloul University Hospital  Sousse Tunisia"},{"name":"Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Zubiaur","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Soria\u2010Chacartegui","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Villapalos\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Candau","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Rodr\u00edguez\u2010Lopez","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Gonz\u00e1lez\u2010Iglesias","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Aldama","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Navares\u2010Gomez","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Omezzine","sequence":"additional","affiliation":[{"name":"Biochemistry Department, LR12SP11 Sahloul University Hospital  Sousse Tunisia"},{"name":"Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Universidad Aut\u00f3noma de Madrid (UAM), Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-8885","authenticated-orcid":false,"given":"Francisco","family":"Abad\u2010Santos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department 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