{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:41:48Z","timestamp":1792557708147,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004690","name":"Minist\u00e8re de la Sant\u00e9","doi-asserted-by":"publisher","award":["PHRCI 2013 API13\/T\/065"],"award-info":[{"award-number":["PHRCI 2013 API13\/T\/065"]}],"id":[{"id":"10.13039\/501100004690","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to describe the pharmacokinetics (PK) of levetiracetam (LEV) in term neonates treated for neonatal seizures secondary to hypoxic\u2013ischemic encephalopathy (HIE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifteen neonates were included and received a loading dose ranging from 30 to 60\u2009mg\/kg followed by eight maintenance doses corresponding to one\u2010fourth of the loading dose every 8\u00a0h. Five blood PK samples were drawn for each neonate: three after the loading dose and two after the last maintenance dose. Data were analysed by a population approach using NONMEM software. The possible relationship between LEV Cmax and AUC from time 0 to 4\u00a0h after the loading dose (AUC\n                      <jats:sub>4h<\/jats:sub>\n                      ) and the relative seizure difference (RSD) that defined the LEV efficacy was investigated by linear regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LEV PK was described by a two\u2010compartment model with allometric scaling based on body weight. Typical values (%IIV) for LEV CL, central and peripheral distribution volume (Vc and Vp) and distribution clearance (Q) were 4.27 (15%) L\/h, 46.5 (14%) L, 6.10\u00a0L (98%) and 1.75\u2009L\/h, respectively. Creatinine clearance (CLcr) and natremia were found to be significant covariates for LEV clearance (CL), CL increasing with CLcr and natremia. No relationship was found between LEV Cmax or AUC\n                      <jats:sub>4h<\/jats:sub>\n                      and RSD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A population PK model of LEV in term neonates with HIE was developed. The influence of natremia was highlighted for the first time and could reflect the relationship between the encephalopathy severity and LEV PK in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70888","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:25:12Z","timestamp":1792556712000},"source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics of levetiracetam in term neonates with hypoxic\u2013ischemic encephalopathy and therapeutic hypothermia: The LEVNEONAT\u20101 study"],"prefix":"10.1002","author":[{"given":"L\u00e9o","family":"Mimram","sequence":"first","affiliation":[{"name":"Pharmacology Unit GHU Paris Seine Saint\u2010 Denis, Assistance Publique\u2010H\u00f4pitaux de Paris  Bondy France"},{"name":"Universit\u00e9 Sorbonne Paris Nord and Universit\u00e9 Paris Cit\u00e9, Inserm, IAME  Paris 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