{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T20:19:43Z","timestamp":1770409183305,"version":"3.49.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Critically ill patients are exposed to important pharmacokinetic alteration that can lead to under- or over-exposure. In addition, children and neonates undergo physical growth and organ maturation that alter drug pharmacokinetics, especially children with sickle cell disease who frequently experience organ dysfunctions. The aim of the study was to describe cefotaxime and desacetyl-cefotaxime pharmacokinetics and optimize dosing regimens in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a pharmacokinetic analysis of cefotaxime and its metabolite desacetyl-cefotaxime via a population approach. Trough concentrations and steady-state concentrations were then simulated using several doses and were compared to pharmacological targets: 100% fT\u200a&amp;gt;\u200a4\u200a\u00d7\u200aMIC and C\u03c4 or CSS &amp;lt; 60\u2005mg\/L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 797 cefotaxime and desacetyl-cefotaxime observations were collected from 242 children and neonates, including 50 with sickle cell disease (SCD). Cefotaxime data was best described by a two-compartment model with first-order absorption and elimination. A supplemental compartment was linked to the cefotaxime central compartment to describe desacetyl-cefotaxime pharmacokinetics. Allometric scaling with bodyweight, eGFR and Sickle cell status turned out to be significant in the model. Post-menstrual age was used to describe organ maturation functions for neonates. Simulations showed that probability of attaining targets was systematically better through continuous perfusion. Doses were suggested up to 300\u2005mg\/kg\/day according to covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified bodyweight, SCD status and eGFR as significant covariate that influence cefotaxime PK. Continuous infusion was the most performant way to achieve the pharmacological target in critically ill children and neonates, making a first necessary step towards individualized prescription in this fragile population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag019","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T12:32:57Z","timestamp":1768048377000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of cefotaxime and its metabolite desacetyl-cefotaxime to optimize dosing in critically ill children and children with sickle cell disease"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-1502","authenticated-orcid":false,"given":"Seef","family":"Abdalla","sequence":"first","affiliation":[{"name":"Inserm, UMR1343, Pharmacologie et \u00e9valuations des th\u00e9rapeutiques chez l'enfant et la femme enceinte, Universit\u00e9 Paris Cit\u00e9 , Paris F-75006 ,","place":["France"]},{"name":"Service de pharmacologie p\u00e9rinatale, p\u00e9diatrique et adulte, AP-HP, H\u00f4pital Cochin , Rue du Faubourg-Saint-Jacques, Paris F-75014 , France"},{"name":"H\u00f4pital Europ\u00e9en Georges Pompidou Service de pharmacologie p\u00e9rinatale, p\u00e9diatrique et adulte, AP-HP, , Rue Leblanc, Paris F-75015 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Royer","sequence":"additional","affiliation":[{"name":"Inserm, UMR1343, Pharmacologie et \u00e9valuations des th\u00e9rapeutiques chez l'enfant et la femme enceinte, Universit\u00e9 Paris Cit\u00e9 , Paris F-75006 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agathe","family":"B\u00e9ranger","sequence":"additional","affiliation":[{"name":"Inserm, UMR1343, Pharmacologie et \u00e9valuations des th\u00e9rapeutiques chez l'enfant et la femme enceinte, Universit\u00e9 Paris Cit\u00e9 , Paris F-75006 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