{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:12:38Z","timestamp":1775707958594,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"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":[[2016,6]]},"abstract":"<jats:sec><jats:title>Aim(s)<\/jats:title><jats:p>Little is known about the pharmacokinetic (PK) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic\u2212ischaemic encephalopathy due to perinatal asphyxia. This study prospectively evaluates and describes the population PK of gentamicin in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Demographic, clinical and laboratory data of patients included in a multicentre prospective observational cohort study (the \u2018PharmaCool Study\u2019) were collected. A non\u2010linear mixed\u2010effects regression analysis (<jats:sc>nonmem<\/jats:sc><jats:sup>\u00ae<\/jats:sup>) was performed to describe the population PK of gentamicin. The most optimal dosing regimen was evaluated based on simulations of the final model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 47 patients receiving gentamicin were included in the analysis. The PK were best described by an allometric two compartment model with gestational age (GA) as a covariate on clearance (CL). During hypothermia the CL of a typical patient (3\u00a0kg, GA 40\u00a0weeks, 2\u00a0days post\u2010natal age (PNA)) was 0.06\u00a0l\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0h<jats:sup>\u22121<\/jats:sup> (inter\u2010individual variability (IIV) 26.6%) and volume of distribution of the central compartment (<jats:italic>V<\/jats:italic><jats:sub>c<\/jats:sub>) was 0.46\u00a0l\u00a0kg<jats:sup>\u22121<\/jats:sup> (IIV 40.8%). CL was constant during hypothermia and rewarming, but increased by 29% after reaching normothermia (&gt;96\u00a0h PNA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study describes the PK of gentamicin in neonates undergoing controlled hypothermia. The 29% higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred. Based on simulations we recommend an empiric dose of 5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> every 36\u00a0h or every 24\u00a0h for patients with GA 36\u201340\u00a0weeks and GA 42\u00a0weeks, respectively.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12883","type":"journal-article","created":{"date-parts":[[2016,1,13]],"date-time":"2016-01-13T22:20:42Z","timestamp":1452723642000},"page":"1067-1077","source":"Crossref","is-referenced-by-count":39,"title":["Altered gentamicin pharmacokinetics in term neonates undergoing controlled hypothermia"],"prefix":"10.1111","volume":"81","author":[{"given":"Yuma A.","family":"Bijleveld","sequence":"first","affiliation":[{"name":"Department of Pharmacy Academic Medical Center  Amsterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo R.","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Emma Children's Hospital Academic Medical Center  Amsterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanneke J. H.","family":"van der Lee","sequence":"additional","affiliation":[{"name":"Pediatric Clinical Research Office, Division Woman\u2010Child, Academic Medical Center University of Amsterdam  Amsterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris","family":"Groenendaal","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Dijk","sequence":"additional","affiliation":[{"name":"Department of Neonatology University Medical Center Groningen  Groningen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arno","family":"van Heijst","sequence":"additional","affiliation":[{"name":"Department of Neonatology Radboud University Medical Center  Nijmegen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogier C. J.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology Erasmus MC\u2010Sophia Children's Hospital  Rotterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen P.","family":"Dijkman","sequence":"additional","affiliation":[{"name":"Department of Neonatology M\u00e1xima Medical Center Veldhoven  Veldhoven"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrica L. M.","family":"van Straaten","sequence":"additional","affiliation":[{"name":"Department of Neonatology Isala Clinics  Zwolle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Rijken","sequence":"additional","affiliation":[{"name":"Department of Neonatology Leiden University Medical Center  Leiden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge A.","family":"Zonnenberg","sequence":"additional","affiliation":[{"name":"Department of Neonatology VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Cools","sequence":"additional","affiliation":[{"name":"Department of Neonatology Vrije Universiteit Brussel  Brussels"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Zecic","sequence":"additional","affiliation":[{"name":"Department of Neonatology Academic Medical Center  Gent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie H. G. M.","family":"Nuytemans","sequence":"additional","affiliation":[{"name":"Clinical Research Coordinator PharmaCool Study"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton H.","family":"van Kaam","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Emma Children's Hospital Academic Medical Center  Amsterdam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron A. 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