{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:42:59Z","timestamp":1791434579475,"version":"4.3.3"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,11,14]],"date-time":"2020-11-14T00:00:00Z","timestamp":1605312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Science and Technology Major Projects"},{"name":"Major New Drugs Innovation and Development","award":["2017ZX09304029-002"],"award-info":[{"award-number":["2017ZX09304029-002"]}]},{"name":"Young Taishan Scholars Programme of Shandong Province"},{"name":"Qilu Young Scholars Programme of Shandong University"},{"name":"Open Fund of Tianjin Central Hospital of Gynecology Obstetrics"},{"name":"Tianjin Key Laboratory of Human Development and Reproductive Regulation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Nowadays, real-world data can be used to improve currently available dosing guidelines and to support regulatory approval of drugs for use in neonates by overcoming practical and ethical hurdles. This proof-of-concept study aimed to assess the population pharmacokinetics of azlocillin in neonates using real-world data, to make subsequent dose recommendations and to test these in neonates with early-onset sepsis (EOS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This prospective, open-label, investigator-initiated study of azlocillin in neonates with EOS was conducted using an adaptive two-step design. First, a maturational pharmacokinetic-pharmacodynamic model of azlocillin was developed, using an empirical dosing regimen combined with opportunistic samples resulting from waste material. Second, a Phase II clinical trial (ClinicalTrials.gov: NCT03932123) of this newly developed model-based dosing regimen of azlocillin was conducted to assure optimized target attainment [free drug concentration above MIC during 70% of the dosing interval (\u201870% fT&amp;gt;MIC\u2019)] and to investigate the tolerance and safety in neonates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A one-compartment model with first-order elimination, using 167 azlocillin concentrations from 95 neonates (31.7\u201341.6\u2009weeks postmenstrual age), incorporating current weight and renal maturation, fitted the data best. For the second step, 45 neonates (30.3\u201341.3\u2009weeks postmenstrual age) were subsequently included to investigate target attainment, tolerance and safety of the pharmacokinetic-pharmacodynamic model-based dose regimen (100\u2009mg\/kg q8h). Forty-three (95.6%) neonates reached their pharmacokinetic target and only two neonates experienced adverse events (feeding intolerance and abnormal liver function), possibly related to azlocillin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Target attainment, tolerance and safety of azlocillin was shown in neonates with EOS using a pharmacokinetic-pharmacodynamic model developed with real-world data.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa468","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T19:11:42Z","timestamp":1603307502000},"page":"699-709","source":"Crossref","is-referenced-by-count":15,"title":["Population pharmacokinetics and dosing optimization of azlocillin in neonates with early-onset sepsis: a real-world study"],"prefix":"10.1093","volume":"76","author":[{"given":"Yue-E","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Liang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Hao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, China"},{"name":"Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, 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