{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T15:17:31Z","timestamp":1771082251136,"version":"3.50.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In the heterogeneous group of preterm and term neonates, gentamicin and tobramycin are mainly dosed according to empirical guidelines, after which therapeutic drug monitoring and subsequent dose adaptation are applied. In view of the variety of neonatal guidelines available, the purpose of this study was to evaluate target concentration attainment of these guidelines, and to propose a new model-based dosing guideline for these drugs in neonates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Demographic characteristics of 1854 neonates (birth weight 390\u20135200 g, post-natal age 0\u201327 days) were extracted from earlier studies and sampled to obtain a test dataset of 5000 virtual patients. Monte Carlo simulations on the basis of validated models were undertaken to evaluate the attainment of target peak (5\u201312 mg\/L) and trough (&amp;lt;0.5 mg\/L) concentrations, and cumulative AUC, with the existing and proposed guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Across the entire neonatal age and weight range, the Dutch National Formulary for Children, the British National Formulary for Children, Neofax and the Red Book resulted in adequate peak but elevated trough concentrations (63%\u201390% above target). The proposed dosing guideline (4.5 mg\/kg gentamicin or 5.5 mg\/kg tobramycin) with a dosing interval based on birth weight and post-natal age leads to adequate peak concentrations with only 33%\u201338% of the trough concentrations above target, and a constant AUC across weight and post-natal age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The proposed neonatal dosing guideline for gentamicin and tobramycin results in improved attainment of target concentrations and should be prospectively evaluated in clinical studies to evaluate the efficacy and safety of this treatment.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkv052","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:32:20Z","timestamp":1426206740000},"page":"2074-2077","source":"Crossref","is-referenced-by-count":49,"title":["Novel model-based dosing guidelines for gentamicin and tobramycin in preterm and term neonates"],"prefix":"10.1093","volume":"70","author":[{"given":"Pyry A. J.","family":"Valitalo","sequence":"first","affiliation":[{"name":"1 \u00a0Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John N.","family":"van den Anker","sequence":"additional","affiliation":[{"name":"2 \u00a0Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA"},{"name":"3 \u00a0Department of Pediatric Pharmacology, University Children's Hospital Basel, Switzerland"},{"name":"4 \u00a0Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[{"name":"5 \u00a0Department of Development and Regeneration, KU Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roosmarijn F. 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P.","family":"Simons","sequence":"additional","affiliation":[{"name":"6 \u00a0Department of Pediatrics, Division of Neonatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"7 \u00a0Department of Medical Microbiology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherijne A. 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