{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:12:26Z","timestamp":1775707946967,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"St. Christopher's Foundation for Children"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Identify population pharmacokinetics and pharmacodynamic target attainment of gentamicin in neonates with hypoxic\u2010ischemic encephalopathy (<jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content>) undergoing controlled hypothermia (<jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Prospective open\u2010label pharmacokinetic study. Gentamicin concentrations were modeled and dosing regimens simulated for a 5000\u2010patient neonatal population with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> using <jats:styled-content style=\"fixed-case\">PM<\/jats:styled-content>etrics, a nonparametric, pharmacometric modeling, and simulation package for R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>A 189\u2010bed children's tertiary care teaching hospital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve patients, 5 (42%) females and 7 (58%) males, met inclusion criteria with a median gestation age of 39.9\u00a0weeks (interquartile range [IQR] 38.5\u201340.2\u00a0wks) and a median birthweight (<jats:styled-content style=\"fixed-case\">BW<\/jats:styled-content>) of 3.3 kg (IQR 3.1\u20133.7 kg). Gentamicin concentrations were best described by a two\u2010compartment model with first\u2010order elimination with <jats:styled-content style=\"fixed-case\">BW<\/jats:styled-content> as a covariate on volume of distribution (Vd). The mean total body population clearance (<jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>) was 2.2\u00a0\u00b1\u00a00.7\u00a0ml\/minute\/kg, and the volume of the central compartment was 0.44\u00a0\u00b1\u00a00.06\u00a0L\/kg. The R<jats:sup>2<\/jats:sup>, bias, and precision for the observed versus population predicted model were 0.917, 1.15, and 10.9\u00a0\u03bcg\/ml; the R<jats:sup>2<\/jats:sup>, bias, and precision for the observed versus individual predicted model were 0.982, \u22120.132, and 0.932\u00a0\u03bcg\/ml, respectively. The calculated mean population estimate for the total Vd was 0.96\u00a0\u00b1\u00a00.4\u00a0L\/kg. The dosing regimen that most consistently produced a maximum concentration (C<jats:sub>max<\/jats:sub>) in the range of 10\u201312\u00a0mg\/L with a minimum concentration (C<jats:sub>min<\/jats:sub>) level less than 2\u00a0mg\/L was 5\u00a0mg\/kg\/dose given every 36\u00a0hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data suggest the population pharmacokinetics of gentamicin in neonates with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> have an increase in gentamicin <jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content> and are different from previous reports in neonates with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> not receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> and\/or neonates without <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content>. This analysis suggests a dosing regimen of 5\u00a0mg\/kg\/dose every 36\u00a0hours results in a gentamicin C<jats:sub>max<\/jats:sub> within the range of 10\u201312\u00a0mg\/L with a C<jats:sub>min<\/jats:sub> lower than 2\u00a0mg\/L, which is appropriate for treating susceptible gram\u2010negative organisms with minimum inhibitory concentrations of 1\u00a0mg\/L or lower.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2186","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T00:03:55Z","timestamp":1539129835000},"page":"1120-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic\u2010Ischemic Encephalopathy Receiving Controlled Hypothermia"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-5574","authenticated-orcid":false,"given":"Jeffrey 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