{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:38:18Z","timestamp":1787647098090,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["40\u201041500\u201098\u20109002"],"award-info":[{"award-number":["40\u201041500\u201098\u20109002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["40\u201041500\u201098\u20109002"],"award-info":[{"award-number":["40\u201041500\u201098\u20109002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48\u2009h of treatment with pharmacokinetic\/pharmacodynamic target attainment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed\u2010effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic\/pharmacodynamic target attainment. The area under the curve\/minimal inhibitory concentration ratio of 400\u2013600\u2009mg*h\/L was used as target range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen patients received vancomycin (median gestational age: 41 [range: 38\u201342] weeks, postnatal age: 4.4 [2.5\u20135.5] days, birth weight: 3.5 [2.3\u20134.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1\u2010compartment model showed the best fit. Vancomycin clearance was 0.17\u2009L\/h, lower than literature values for term neonates of 3.5\u00a0kg without perinatal asphyxia (range: 0.20\u20130.32\u2009L\/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24\u2009h of treatment. A loading dose of 10\u00a0mg\/kg followed by 24\u2009mg\/kg\/day in 4 doses resulted in target attainment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model\u2010informed precision dosing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16026","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:14:53Z","timestamp":1709810093000},"page":"1418-1427","source":"Crossref","is-referenced-by-count":5,"title":["Population pharmacokinetics of vancomycin in term neonates with perinatal asphyxia treated with therapeutic hypothermia"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2600-1381","authenticated-orcid":false,"given":"Marlotte A. A.","family":"van der Veer","sequence":"first","affiliation":[{"name":"Department of Pharmacy &amp; Clinical Pharmacology Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo R.","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Emma Children's Hospital Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-9825","authenticated-orcid":false,"given":"Linda G. W.","family":"Franken","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Clinical Pharmacology Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinier M.","family":"van Hest","sequence":"additional","affiliation":[{"name":"Department of Pharmacy &amp; Clinical Pharmacology Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Groenendaal","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children's Hospital  Utrecht The Netherlands"},{"name":"UMC Utrecht Brain Center University Medical Center Utrecht and Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Dijk","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatrics, Division of Neonatology University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem P.","family":"de Boode","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Radboud University Medical Center, Radboud Institute for Health Sciences Amalia Children's Hospital  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinno","family":"Simons","sequence":"additional","affiliation":[{"name":"Department of Neonatal and Pediatric Intensive Care, Division of Neonatology Erasmus MC\u2010Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen P.","family":"Dijkman","sequence":"additional","affiliation":[{"name":"Department of Neonatology M\u00e1xima Medical Center Veldhoven  Veldhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrica L. M.","family":"van Straaten","sequence":"additional","affiliation":[{"name":"Department of Neonatology Isala Clinics  Zwolle The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Rijken","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Willem\u2010Alexander Children's Hospital Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Cools","sequence":"additional","affiliation":[{"name":"Department of Neonatology Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie H. G. 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