{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T21:53:06Z","timestamp":1776894786420,"version":"3.51.2"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T00:00:00Z","timestamp":1490832000000},"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":[[2017,4]]},"abstract":"<jats:sec><jats:title>Study Objective<\/jats:title><jats:p>To describe the population pharmacokinetics and pharmacodynamic target attainment of ampicillin 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>A 189\u2010bed, freestanding children's tertiary care teaching hospital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Thirteen neonates (three females and 10 males) with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> encephalopathy receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> and ampicillin 100 mg\/kg\/dose intravenously every 8 hours who were admitted to the neonatal intensive care unit between May 2013 and June 2014.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Blood (0.5 ml) was collected at 8, 10, and 14 hours of life coinciding with other scheduled laboratory investigations for ampicillin concentration analysis, providing a total of three ampicillin serum concentrations\/patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>The patients had a median gestational age of 39 weeks, mean \u00b1 <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> birth weight of 3.34 \u00b1 0.61 kg, and mean \u00b1 <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> estimated glomerular filtration rate of 43 \u00b1 12.6 ml\/minute\/1.73 m<jats:sup>2<\/jats:sup>. Ampicillin concentrations were best described by a two\u2010compartment model with gestational age as a covariate with allometric scaling on total body clearance. The mean \u00b1 <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content> total body clearance for the population was 0.43 \u00b1 0.12 ml\/minute\/kg (median 0.36 ml\/min\/kg), volume of the central compartment was 0.35 \u00b1 0.46 L\/kg, and the calculated population estimate for the total volume of distribution (V<jats:sub>d<\/jats:sub>) was 0.52 \u00b1 0.28 L\/kg. The <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>, bias, and precision were 0.497, 0.538, and 10.5 \u03bcg\/ml and 0.972, \u22120.125, and 0.938 \u03bcg\/ml for the observed versus population and observed versus individual predicted concentrations, respectively. Monte Carlo simulation was conducted to determine the probability of target attainment for 12 simulated ampicillin dosing regimens using 50% and 100% of the dosing interval that free drug concentration remains above the minimum inhibitory concentration (<jats:styled-content style=\"fixed-case\"><jats:italic>f<\/jats:italic>T<\/jats:styled-content> &gt; <jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>) in 5000 simulated neonates with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>. Dosing regimens of 25 and 50 mg\/kg\/dose every 24 hours provided for an appropriate pharmacodynamic target attainment of 50% and 100% <jats:styled-content style=\"fixed-case\"><jats:italic>f<\/jats:italic>T<\/jats:styled-content> &gt; MIC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To our knowledge, this study describes the first pharmacokinetic data of ampicillin in neonates with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> and demonstrates a reduced total body clearance and an increased V<jats:sub>d<\/jats:sub> for ampicillin. Based on these data, modifications to the ampicillin dosing regimens seem appropriate during the period of <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content>. Dosing regimens of ampicillin 25 and 50 mg\/kg\/day were able achieve optimal probability of target attainment against all susceptible gram\u2010negative and gram\u2010positive bacteria in a population of neonates with <jats:styled-content style=\"fixed-case\">HIE<\/jats:styled-content> receiving <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> for 50% and 100% <jats:styled-content style=\"fixed-case\"><jats:italic>f<\/jats:italic>T<\/jats:styled-content> &gt; <jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1916","type":"journal-article","created":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T18:16:42Z","timestamp":1487787402000},"page":"456-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Population Pharmacokinetics and Pharmacodynamic Target Attainment of Ampicillin in Neonates with Hypoxemic\u2010Ischemic Encephalopathy in the Setting of Controlled Hypothermia"],"prefix":"10.1002","volume":"37","author":[{"given":"Jeffrey J.","family":"Cies","sequence":"first","affiliation":[{"name":"The Center for Pediatric Pharmacotherapy LLC Pottstown Pennsylvania"},{"name":"St. Christopher's Hospital for Children Philadelphia Pennsylvania"},{"name":"Drexel University College of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keri N.","family":"Fugarolas","sequence":"additional","affiliation":[{"name":"St. Christopher's Hospital for Children Philadelphia Pennsylvania"},{"name":"Drexel University College of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Wayne S.","family":"Moore","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Pharmacotherapy LLC Pottstown Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert W.","family":"Mason","sequence":"additional","affiliation":[{"name":"Alfred I. DuPont Hospital for Children Wilmington Delaware"},{"name":"Nemours Biomedical Research Wilmington Delaware"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ogechukwu R.","family":"Menkiti","sequence":"additional","affiliation":[{"name":"St. Christopher's Hospital for Children Philadelphia Pennsylvania"},{"name":"Drexel University College of Medicine Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(02)01959-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2002.023093"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-8-17"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2004.06.014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17946-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcps050929"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0456"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.03.030"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.146"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000281517.97507.6E"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.39.1.97"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825c4ba6"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01117450"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23574"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj070248"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.3.333"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01640309"},{"key":"e_1_2_7_19_1","unstructured":"Claris Lifesciences Inc.Ampicillin package insert.North Brunswick NJ;2010."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2005.11.007"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/514622"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1542\/peds.39.2.194","article-title":"Serum levels of methicillin and ampicillin in newborn and premature infants in relation to postnatal age","volume":"39","author":"Boe RW","year":"1967","journal-title":"Pediatrics"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02374-13"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1997.tb14802.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000146517.17910.54"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2003.09.017"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.17228"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2009.192"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.2165\/11319360-000000000-00000"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1916","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.1916","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:14:19Z","timestamp":1761041659000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.1916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,30]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,4]]}},"alternative-id":["10.1002\/phar.1916"],"URL":"https:\/\/doi.org\/10.1002\/phar.1916","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,30]]},"assertion":[{"value":"2017-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}