{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T13:46:59Z","timestamp":1782481619536,"version":"3.54.5"},"reference-count":26,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"EuroELSO","award":["Euro ELSO Grant 2023\/Reg.no. 09335480"],"award-info":[{"award-number":["Euro ELSO Grant 2023\/Reg.no. 09335480"]}]},{"name":"Ministry of Health, Czech Republic \u2013 conceptual development of research organization","award":["DRO-VFN64165"],"award-info":[{"award-number":["DRO-VFN64165"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Perfusion"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>There is a lack of data supporting rationale drug use with extracorporeal membrane oxygenation (ECMO). The aim of this study was to externally validate a previously developed population pharmacokinetic model of meropenem in neonatal ECMO and continuous renal replacement therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of twenty-eight neonates with a body weight of 3.81 (3.45\u20134.11) kg, median (interquartile) and a postnatal age of 3 (2\u20134) days were enrolled. One hundred plasma concentrations of meropenem were used for external validation by a published population pharmacokinetic analysis model using NONMEM V7.3.0 (ICON Development Solutions, Ellicott City, MD, USA) and PsN v3.4.2, both running in Pirana 2.9.0. Prediction error analyses, and NPDE diagnostics were performed to assess the model\u2019s extrapolative capability. Bayesian forecasting was conducted to determine the impact of prior concentration information on predictive performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Population-based predictions showed minimal overall bias but limited accuracy, with substantial variability between predicted and observed concentrations and less than half of predictions falling within an acceptable deviation range. After incorporating one prior measured concentration through Bayesian forecasting, predictive performance improved markedly. Most predictions were then close to the values observed, and overall accuracy increased substantially.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The meropenem population pharmacokinetic model provides unbiased but imprecise population-level predictions and is therefore not suitable for a priori dosing in neonatal ECMO patients. Including just one prior concentration greatly improves prediction, supporting the use of this model for Bayesian, therapeutic drug monitoring\u2013guided dosing of meropenem in this vulnerable population. (The study identification number is K 2026-0116).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02676591261462288","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:10:35Z","timestamp":1782220235000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["External validation of the population pharmacokinetic model of meropenem in patients undergoing neonatal extracorporeal membrane oxygenation and continuous renal replacement therapy"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6803-7350","authenticated-orcid":false,"given":"Pavla","family":"Pokorn\u00e1","sequence":"first","affiliation":[{"name":"Charles University"},{"name":"Karolinska Institutet"},{"name":"Department of Pediatric Surgery, Erasmus Medical Centre Sophia Children\u2019s Hospital, Rotterdam, The Netherlands"},{"name":"Karolinska University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Michali\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Charles University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"B\u011blohl\u00e1vek","sequence":"additional","affiliation":[{"name":"2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine Charles University and General University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1235-4776","authenticated-orcid":false,"given":"Jonas","family":"Berner","sequence":"additional","affiliation":[{"name":"Charles University"},{"name":"Karolinska Institutet"},{"name":"Karolinska University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"e_1_3_5_2_2","first-page":"80","article-title":"Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support in infancy","volume":"22","author":"Bartlett RH","year":"1976","unstructured":"Bartlett RH, Gazzaniga AB, Jefferies MR, et al. Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support in infancy. Trans Am Soc Artif Intern Organs 1976; 22: 80\u201393.","journal-title":"Trans Am Soc Artif Intern Organs"},{"issue":"7","key":"e_1_3_5_3_2","first-page":"20130321","article-title":"The ECMO PK project: an incremental research approach to advance understanding of the pharmacokinetic alterations and improve patient outcomes during extracorporeal membrane oxygenation","volume":"13","author":"Shekar K","year":"2013","unstructured":"Shekar K, Roberts JA, Smith MT, et al. The ECMO PK project: an incremental research approach to advance understanding of the pharmacokinetic alterations and improve patient outcomes during extracorporeal membrane oxygenation. 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Population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically ill young children. J Pediatr Pharmacol Therapeut 2017; 22: 276\u2013285. https:\/\/doi.org\/10.5863\/1551-6776-22.4.276","journal-title":"J Pediatr Pharmacol Therapeut"},{"key":"e_1_3_5_16_2","first-page":"20240503","article-title":"Meropenem disposition in neonatal and pediatric extracorporeal membrane oxygenation and continuous renal replacement therapy","volume":"13","author":"Pokorna P","year":"2024","unstructured":"Pokorna P, Michalickova D, Tibboel D, et al. Meropenem disposition in neonatal and pediatric extracorporeal membrane oxygenation and continuous renal replacement therapy. Antibiotics (Basel) 2024; 13: 20240503. https:\/\/doi.org\/10.3390\/antibiotics13050419","journal-title":"Antibiotics (Basel)"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01060893"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13010043"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2007.12.002"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-025-03875-x"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.709332"},{"key":"e_1_3_5_24_2","first-page":"92","article-title":"Pharmacokinetics of continuous infusion meropenem with concurrent extracorporeal life support and continuous renal replacement therapy: a case report","volume":"21","author":"Cies JJ","year":"2016","unstructured":"Cies JJ, Moore WS2nd, Conley SB, et al. 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