{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:12:14Z","timestamp":1775707934564,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec><jats:title>Study Objective<\/jats:title><jats:p>To evaluate the pharmacokinetics of gentamicin in neonates with hypoxic ischemic encephalopathy (<jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content>) receiving hypothermia and to identify an empiric gentamicin dosing strategy in this population that optimizes achievement of target peak and trough concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Population pharmacokinetic study using retrospective medical record data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Tertiary neonatal intensive care unit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>A total of 29 full\u2010term neonates diagnosed with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> treated with hypothermia who received gentamicin and underwent therapeutic drug monitoring<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurement and Main Results<\/jats:title><jats:p>Patient demographics and gentamicin concentration data were retrospectively collected over a 2\u2010year period. A population\u2010based pharmacokinetic model was developed using nonlinear mixed\u2010effects modeling (NONMEM). Using the developed model, Monte Carlo simulations were performed to evaluate the probability of achieving target peak (&gt;\u00a06\u00a0mg\/L) and trough (&lt;\u00a02\u00a0mg\/L) gentamicin concentrations for various potential dosing regimens. A one\u2010compartment model best described the available gentamicin concentration data. Birthweight and serum creatinine significantly influenced gentamicin clearance. For the typical study neonate (birthweight 3.3\u00a0kg, serum creatinine 0.9\u00a0mg\/dl), clearance was 0.034\u00a0L\/hour\/kg and volume was 0.52\u00a0L\/kg. At a 24\u2010hour dosing interval, Monte Carlo simulations predicted target gentamicin peak and trough concentrations could not be reliably achieved at any dose. At a 36\u2010hour dosing interval, a dose of 4\u20135\u00a0mg\/kg is predicted to achieve target gentamicin peak and trough concentrations in more than\u00a090% of neonates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gentamicin clearance is decreased in neonates with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> treated with hypothermia compared with previous reports in nonasphyxiated normothermic full\u2010term neonates. A prolonged 36\u2010hour dosing interval will be needed to achieve target gentamicin trough concentrations in this population. Further prospective evaluation of this dosing recommendation is needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1263","type":"journal-article","created":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T08:54:01Z","timestamp":1364806441000},"page":"718-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Gentamicin Pharmacokinetics and Dosing in Neonates with Hypoxic Ischemic Encephalopathy Receiving Hypothermia"],"prefix":"10.1002","volume":"33","author":[{"given":"Adam","family":"Frymoyer","sequence":"first","affiliation":[{"name":"Department of Pediatrics Stanford University Palo Alto California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Stanford Hospital and Clinics Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia L.","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Verotta","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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