{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:14:50Z","timestamp":1789456490886,"version":"build-2803163510"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005609","name":"University of Turku","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005609","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Methylprednisolone is used during paediatric cardiac surgery with cardiopulmonary bypass to attenuate the systemic inflammatory response. However, developmental differences in drug disposition and cardiopulmonary bypass\u2013related factors contribute to pharmacokinetic variability in this population. We aimed to develop a population pharmacokinetic model of methylprednisolone in neonates and paediatric patients undergoing cardiac surgery with cardiopulmonary bypass and to identify factors associated with its pharmacokinetic variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data were pooled from four prospective clinical studies including 93 patients aged 1 to 574 days undergoing cardiac surgery with cardiopulmonary bypass. Methylprednisolone was administered as an intravenous bolus after anaesthesia induction or into the cardiopulmonary bypass circuit at 5 or 30\u00a0mg\/kg. Plasma concentrations were measured perioperatively. A nonlinear mixed-effects model was developed using NONMEM. Covariate effects were evaluated. Model evaluation included goodness-of-fit plots, normalized prediction distribution errors, sampling importance resampling, and prediction-corrected visual predictive checks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A one-compartment model with first-order elimination adequately described the data. The final model identified body weight, an empirical postmenstrual-age effect on clearance, and operation-group differences in the apparent volume of distribution as significant determinants of methylprednisolone pharmacokinetics. Interindividual variability was estimated for clearance (48.1%) and volume of distribution (19.9%). Model evaluation supported the predictive performance of the final model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We developed a population pharmacokinetic model for methylprednisolone in paediatric patients undergoing cardiac surgery with cardiopulmonary bypass. The model identifies body weight, postmenstrual age and operation group as determinants of pharmacokinetic variability. It provides a descriptive framework for characterizing methylprednisolone disposition in this heterogeneous population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number and date<\/jats:title>\n                    <jats:p>EudraCT 2008-007413-76 2008-12-23.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-026-04168-7","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:10Z","timestamp":1787026510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics of methylprednisolone in neonates and paediatric patients undergoing cardiac surgery with cardiopulmonary bypass"],"prefix":"10.1007","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3200-0649","authenticated-orcid":false,"given":"Matias","family":"Rantanen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juho","family":"Keski-Nisula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-8665","authenticated-orcid":false,"given":"Klaus T.","family":"Olkkola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-9411","authenticated-orcid":false,"given":"Pertti J.","family":"Neuvonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9624-3063","authenticated-orcid":false,"given":"Eero","family":"Pesonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pertti","family":"Suominen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-4561","authenticated-orcid":false,"given":"Teijo I.","family":"Saari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"4168_CR1","doi-asserted-by":"publisher","first-page":"S715","DOI":"10.1016\/s0003-4975(02)04701-x","volume":"75","author":"JH Levy","year":"2003","unstructured":"Levy JH, Tanaka KA (2003) Inflammatory response to cardiopulmonary bypass. 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