{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T11:37:40Z","timestamp":1792237060790,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Develop a population pharmacokinetic model describing propofol pharmacokinetics in (pre)term neonates and infants, that can be used for precision dosing (e.g. during target\u2010controlled infusion) of propofol in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A nonlinear mixed effects pharmacokinetic analysis (Monolix 2018R2) was performed, based on a pooled study population in 107 (pre)term neonates and infants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 836 blood samples were collected from 66 (pre)term neonates and 41 infants originating from 3 studies. Body weight (BW) of the pooled study population was 3.050 (0.580\u201311.440) kg, postmenstrual age (PMA) was 36.56 (27.00\u201343.00) weeks and postnatal age (PNA) was 1.14 (0\u2013104.00) weeks (median and min\u2010max range). A 3\u2010compartment structural model was identified and the effect of BW was modelled using fixed allometric exponents. Elimination clearance maturation was modelled accounting for the maturational effect on elimination clearance until birth (by gestational age [GA]) and postpartum (by PNA and GA). The extrapolated adult (70 kg) population propofol elimination clearance (1.64 L min<jats:sup>\u22121<\/jats:sup>, estimated relative standard error = 6.02%) is in line with estimates from previous population pharmacokinetic studies. Empirical scaling of BW on the central distribution volume in function of PNA improved the model fit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>It is recommended to describe elimination clearance maturation by GA and PNA instead of PMA on top of size effects when analyzing propofol pharmacokinetics in populations including preterm neonates. Changes in body composition in addition to weight changes or other physio\u2010anatomical changes may explain the changes in central distribution volume. The developed model may serve as a prior for propofol dose finding and target\u2010controlled infusion in (preterm) neonates.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14620","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T19:25:29Z","timestamp":1603308329000},"page":"2089-2097","source":"Crossref","is-referenced-by-count":16,"title":["Population pharmacokinetics of propofol in neonates and infants: Gestational and postnatal age to determine clearance maturation"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-289X","authenticated-orcid":false,"given":"Louis","family":"Sandra","sequence":"first","affiliation":[{"name":"Drug Delivery and Disposition KU Leuven Department of Pharmaceutical and Pharmacological Sciences  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Smits","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Development and Regeneration  Leuven Belgium"},{"name":"Neonatal Intensive Care Unit University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Development and Regeneration  Leuven Belgium"},{"name":"Division of Clinical Pharmacy Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-0085","authenticated-orcid":false,"given":"Johan","family":"Nicola\u00ef","sequence":"additional","affiliation":[{"name":"Development Science UCB BioPharma SPRL, Braine\u2010l'Alleud  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition KU Leuven Department of Pharmaceutical and Pharmacological Sciences  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bouillon","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition KU Leuven Department of Pharmaceutical and Pharmacological Sciences  Leuven Belgium"},{"name":"Bionotus, Niel  Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"European Medicines Agency.Revised priority list for studies on off\u2010patent paediatric medicinal products. Published online August 2013. Accessed July 24 2019.https:\/\/www.ema.europa.eu\/en\/documents\/other\/revised-priority-list-studies-patent-paediatric-medicinal-products_en.pdf"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pan.13706"},{"key":"e_1_2_10_4_1","unstructured":"Aspen Pharmacare Canada Inc.Propofol Product Monograph. Published online August 8 2017. Accessed July 24 2019. pdf.hres.ca\/dpd_pm\/00040632.PDF"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-814647-7.00007-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/80.6.788"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0681-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2005.12.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035092"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aem294"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1214"},{"issue":"6","key":"e_1_2_10_12_1","first-page":"1570","article-title":"A bodyweight\u2010dependent Allometric exponent for scaling clearance across the human life\u2010span","volume":"29","author":"Wang C","year":"2012","journal-title":"Pharmaceutical"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.01.018"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aer198"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.07.049"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-003-0585-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13160"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23574"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13230"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/10.2.290"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-018-9607-8"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200212000-00010"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0672-3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aen276"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-012-0109-6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/63.6.667"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeh042"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1989.tb03548.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.043752"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.2.259"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0277-z"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544100-00004"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2018.04.001"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14620","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.14620","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.14620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T05:52:18Z","timestamp":1693288338000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.14620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,20]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1111\/bcp.14620"],"URL":"https:\/\/doi.org\/10.1111\/bcp.14620","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,20]]}}}