{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:55:01Z","timestamp":1781535301156,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxic\u2010ischemic encephalopathy (HIE) resulting from perinatal asphyxia presents a substantial risk of mortality and long\u2010term sequelae in neonates. Therapeutic hypothermia (TH) improves both short\u2010 and long\u2010term outcomes in near\u2010term\/term neonates with moderate to severe HIE. While neonates with perinatal asphyxia and TH often require polypharmacy, the impact of both covariates on pharmacokinetics and pharmacodynamics is only partially described and quantified. In this pooled, multicenter retrospective study, longitudinal trends of human serum albumin (HSA, the major drug binding protein) and total protein (TP) concentrations in near\u2010term\/term neonates were described using linear mixed models and compared between cohorts (TH vs control neonates, and moderate vs severe HIE TH cases). A mathematical function for HSA concentrations in neonates with HIE undergoing TH was derived (AlbuCool function). The pooled dataset to estimate these functions contained 330 TH neonates and 425 controls with 1725 and 1415 HSA observations, respectively. The median (interquartile range) HSA concentration was 27.0 (23.0\u201031.0) g\/L for the TH cohort, and 32.1 (28.4\u201035.7) g\/L for the control cohort. Estimated mean HSA concentrations were significantly lower (<jats:italic>P<\/jats:italic> &lt;\u00a0.001) in TH compared to control cases, as well as in severe compared to moderate HIE cases (<jats:italic>P<\/jats:italic> &lt;\u00a0.001) over the first 7 postnatal days. The HSA function for neonates with HIE undergoing TH was: HSA (g\/L) = 32.28 \u2212 2.94 * PNA + 0.33 * PNA<jats:sup>2<\/jats:sup> (PNA is postnatal age). The integration of this function in pharmacokinetic models holds the promise to improve the predictive performance of these models, and consequently, the pharmacotherapy of HSA\u2010bound drugs in this vulnerable population.<\/jats:p>","DOI":"10.1002\/jcph.70003","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:43:17Z","timestamp":1739263397000},"page":"923-932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mathematical Albumin Function for Neonates Undergoing Therapeutic Hypothermia in Comparison with Control Neonates"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3060-6719","authenticated-orcid":false,"given":"Zo\u00eb","family":"Vander Elst","sequence":"first","affiliation":[{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"},{"name":"Neonatal Intensive Care Unit University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Stultjens","sequence":"additional","affiliation":[{"name":"Faculty of Medicine KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Clarke","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit Norfolk and Norwich University Hospitals NHS Foundation Trust  Norwich UK"},{"name":"Norwich Medical School University of East Anglia  Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabek","family":"Iglesias\u2010Platas","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit Norfolk and Norwich University Hospitals NHS Foundation Trust  Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1864-3809","authenticated-orcid":false,"given":"Elisabeth","family":"Agathos","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit Norfolk and Norwich University Hospitals NHS Foundation Trust  Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gozdem","family":"Kayk\u0131","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annouschka","family":"Laenen","sequence":"additional","affiliation":[{"name":"Leuven Biostatistics and Statistical Bioinformatics Centre (L\u2010Biostat) KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadir","family":"Yal\u00e7\u0131n","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"},{"name":"Neonatal Intensive Care Unit University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-5105","authenticated-orcid":false,"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"},{"name":"Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"},{"name":"Department of Hospital Pharmacy Erasmus MC  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organisation.Newborn mortality. Accessed April 17 2024.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/levels\u2010and\u2010trends\u2010in\u2010child\u2010mortality\u2010report\u20102021#:~:text=There%20are%20approximately%206700%20newborn in%20child%20survival%20since%201990"},{"key":"e_1_2_11_3_1","article-title":"Birth asphyxia","author":"Gillam\u2010Krakauer M","year":"2024","journal-title":"StatPearls"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003311.pub3"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378\u20103782(91)90191\u20105"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201064029\u20101.00010\u20102"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651\u20102227.1997.tb08581.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1976.00500100030012"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2016\/22896.8882"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.03.014"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103476(81)80555\u20100"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e31811eba5e"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/fms005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010017\u20102165\u20103"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00587"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14958"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035092"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.06.004"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096\u2010018\u20103277\u20108"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13899"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010017\u20102956\u20102"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/children11010072"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010024\u201003634\u20101"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41372\u2010021\u201000987\u2010x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/85.4.599"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894\u2010021\u201000813\u20106"},{"key":"e_1_2_11_27_1","unstructured":"Repository of modeling publications. Accessed October 7 2024.https:\/\/www.melinda\u2010dosing.com\/for%20modelers"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811209023119"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2023.2237412"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000525574"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21916"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2021.05.018"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010012\u20100018\u20105"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010024\u201001403\u20101"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17745"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096\u2010012\u20101703\u2010x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01185\u201015"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9945424"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004563215599560"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2015.12.243"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-024-03094-7"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T01:57:15Z","timestamp":1750989435000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/jcph.70003"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70003","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]},"assertion":[{"value":"2024-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}