{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:18:25Z","timestamp":1790432305010,"version":"4.1.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Innovational Research Incentives Scheme, Dutch Organization for Scientific Research"},{"name":"Agency for Innovation by Science and Technology in Flanders","award":["IWT\/SBO 130033"],"award-info":[{"award-number":["IWT\/SBO 130033"]}]},{"DOI":"10.13039\/501100004522","name":"Top Institute Pharma","doi-asserted-by":"publisher","award":["D2-104"],"award-info":[{"award-number":["D2-104"]}],"id":[{"id":"10.13039\/501100004522","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations. Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published data set, we assessed the impact of PATH on amikacin PK by using population modeling. Monte Carlo and stochastic simulations were performed to establish amikacin exposures in neonates with PATH after dosing according to the current guidelines and according to proposed model-derived dosing guidelines. Amikacin clearance was decreased 40.6% in neonates with PATH, with no changes in volume of distribution. Simulations showed that increasing the dosing interval by 12 h results in a decrease in the percentage of neonates reaching toxic trough levels (&gt;5 mg\/liter), from 40 to 76% to 14 to 25%, while still reaching efficacy targets compared to the results of current dosing regimens. Based on this study, a 12-h increase in the amikacin dosing interval in neonates with PATH is proposed to correct for the reduced clearance, yielding safe and effective exposures. As amikacin is renally excreted, further studies into other renally excreted drugs may be required, as their clearance may also be impaired.<\/jats:p>","DOI":"10.1128\/aac.01282-17","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T00:50:18Z","timestamp":1507596618000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia"],"prefix":"10.1128","volume":"61","author":[{"given":"Sinziana","family":"Cristea","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Leiden Academic Centre of Drug Research, Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Smits","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"},{"name":"Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Kulo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Sarajevo, Sarajevo, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherijne A. J.","family":"Knibbe","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Leiden Academic Centre of Drug Research, Leiden University, Leiden, The Netherlands"},{"name":"Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"van Weissenbruch","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke H. J.","family":"Krekels","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Leiden Academic Centre of Drug Research, Leiden University, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[{"name":"Intensive Care, Department of Pediatric Surgery, and Department of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands"},{"name":"Department of Development and Regeneration, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140120-00004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01157-15"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2017.1234606"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.146"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/11319360-000000000-00000"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612821666150901110929"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000403893.61640.b6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2013.59"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-014-1527-z"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000014195"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/11595640-000000000-00000"},{"key":"e_1_3_3_13_2","first-page":"106","article-title":"Model evaluation in nonlinear mixed effect models, with applications to pharmacokinetics","volume":"151","author":"Comets E","year":"2010","unstructured":"Comets E BrendelK Mentr\u00e9F. 2010. Model evaluation in nonlinear mixed effect models, with applications to pharmacokinetics. J Soc Fr Stat151:106\u2013127.","journal-title":"J Soc Fr Stat"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-1197-y"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198510000-00014"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-2942"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900854"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12883"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000014053"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0101-6"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01282-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01282-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:46:54Z","timestamp":1645476414000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01282-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1128\/AAC.01282-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01282-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"2017-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01282-17"}}