{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:12:13Z","timestamp":1788048733466,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Progres Q25"],"award-info":[{"award-number":["Progres Q25"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15\u201320 mg\/kg followed by a maintenance dose of 3\u20135 mg\/kg\/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.<\/jats:p>","DOI":"10.3390\/pharmaceutics13030301","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T04:36:24Z","timestamp":1614314184000},"page":"301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-738X","authenticated-orcid":false,"given":"Martin","family":"\u0160\u00edma","sequence":"first","affiliation":[{"name":"Department of Pharmacology, First Faculty of Medicine, Charles University, 110 00 Prague, Czech Republic"},{"name":"General University Hospital in Prague, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9690-9846","authenticated-orcid":false,"given":"Danica","family":"Michali\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, First Faculty of Medicine, Charles University, 110 00 Prague, Czech Republic"},{"name":"General University Hospital in Prague, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-7562","authenticated-orcid":false,"given":"Ond\u0159ej","family":"Slana\u0159","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, First Faculty of Medicine, Charles University, 110 00 Prague, Czech Republic"},{"name":"General University Hospital in Prague, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F70","DOI":"10.1136\/fn.78.1.F70","article-title":"Neonatal seizures","volume":"78","author":"Evans","year":"1998","journal-title":"Arch. 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