{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:15:52Z","timestamp":1790363752141,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003132","name":"Agentschap voor Innovatie door Wetenschap en Technologie","doi-asserted-by":"publisher","award":["IWT\/SBO 130033"],"award-info":[{"award-number":["IWT\/SBO 130033"]}],"id":[{"id":"10.13039\/501100003132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Lisinopril is an angiotensin converting enzyme inhibitor to treat hypertension. It shows complex pharmacokinetics (PK), and its PK behaviour in paediatric populations is not well characterized. The aim of this study was to develop a physiologically based PK (PBPK) model for lisinopril to describe the drug's PK in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The PBPK model development was performed in a step\u2010wise manner. An adult model was initially developed to characterize lisinopril's disposition and absorption and verified using literature data. Subsequently, the adult PBPK model was extrapolated to the paediatric population (0.5\u201318 years old) by accounting for age\u2010dependent physiological and anatomical changes. Model performance was evaluated by comparing the PK profiles and drug exposures of observed<jats:italic>vs<\/jats:italic>predicted data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The disposition of lisinopril was well described by a minimal PBPK model\u2014an effective strategy to capture the biphasic elimination of the drug. The absorption of lisinopril was described by the intestinal peptide transporter\u2010mediated uptake. The adult model adequately described the literature data with predictions within a twofold range of clinical observations. Good model predictivity was also observed in children older than 6 years of age. The model overpredicted the drug exposure in children under 6 years, probably due to not incorporating the actual, unknown ontogeny of the intestinal peptide transporter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The PBPK model predicted the PK of lisinopril in adults and children above 6 years of age well. Model refinement in children under 6 years warrants future informative ontogeny data of the intestinal peptide transporter.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14492","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T21:59:49Z","timestamp":1595368789000},"page":"1203-1214","source":"Crossref","is-referenced-by-count":13,"title":["Physiologically based pharmacokinetic modelling of lisinopril in children: A case story of angiotensin converting enzyme inhibitors"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9038-2676","authenticated-orcid":false,"given":"Feifan","family":"Xie","sequence":"first","affiliation":[{"name":"Division of Biopharmaceutics and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences Central South University Changsha China"},{"name":"Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Van Bocxlaer","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00196112"},{"key":"e_1_2_10_3_1","unstructured":"EMA.Europa.eu. 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