{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:50:59Z","timestamp":1782255059924,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:00:00Z","timestamp":1582588800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seattle Children\u2019s Hospital Academic Enrichment Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Anesthesiology Research and Practice"],"published-print":{"date-parts":[[2020,2,25]]},"abstract":"<jats:p>Dexmedetomidine is a promising sedative and analgesic for newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Pharmacokinetics and safety of dexmedetomidine were evaluated in a phase I, single-center, open-label study to inform future trial strategies. We recruited 7 neonates \u226536 weeks\u2019 gestational age diagnosed with moderate-to-severe HIE, who received a continuous dexmedetomidine infusion during TH and the 6\u2009h rewarming period. Time course of plasma dexmedetomidine concentration was characterized by serial blood sampling during and after the 64.8\u2009\u00b1\u20096.9 hours of infusion. Noncompartmental analysis yielded descriptive pharmacokinetic estimates: plasma clearance of 0.760\u2009\u00b1\u20090.155\u2009L\/h\/kg, steady-state distribution volume of 5.22\u2009\u00b1\u20092.62\u2009L\/kg, and mean residence time of 6.84\u2009\u00b1\u20093.20\u2009h. Naive pooled and population analyses according to a one-compartment model provided similar estimates of clearance and distribution volume. Overall, clearance was either comparable or lower, distribution volume was larger, and mean residence time or elimination half-life was longer in cooled newborns with HIE compared to corresponding estimates previously reported for uncooled (normothermic) newborns without HIE at comparable gestational and postmenstrual ages. As a result, plasma concentrations in cooled newborns with HIE rose more slowly in the initial hours of infusion compared to predicted concentration-time profiles based on reported pharmacokinetic parameters in normothermic newborns without HIE, while similar steady-state levels were achieved. No acute adverse events were associated with dexmedetomidine treatment. While dexmedetomidine appeared safe for neonates with HIE during TH at infusion doses up to 0.4\u2009<jats:italic>\u03bc<\/jats:italic>g\/kg\/h, a loading dose strategy may be needed to overcome the initial lag in rise of plasma dexmedetomidine concentration.<\/jats:p>","DOI":"10.1155\/2020\/2582965","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T18:30:57Z","timestamp":1582655457000},"page":"1-15","source":"Crossref","is-referenced-by-count":17,"title":["Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-1698","authenticated-orcid":true,"given":"Ryan M.","family":"McAdams","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pak","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Seattle Children\u2019s Hospital, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojan","family":"Lalovic","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Sciences, Eisai Inc., Woodcliff Lake, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Phillips","sequence":"additional","affiliation":[{"name":"Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny D.","family":"Shen","sequence":"additional","affiliation":[{"name":"Pharmacokinetics Laboratory, Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, 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