{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:16:49Z","timestamp":1753877809441,"version":"3.41.2"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Institutional Research Grant of Christian Medical College, Vellore, India"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>With current recommendation for phenobarbitone dosing, we have noted that babies are extremely sedated with elevated serum phenobarbitone levels. We postulate that asphyxiated neonates with hypoxic liver injury have impaired drug metabolism and renal injury affects drug elimination, thus elevating serum drug levels. Therapeutic hypothermia (TH) could further affect the drug levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine the serum levels of the phenobarbitone in babies receiving different loading doses of phenobarbitone for neonatal seizures and to study the effect of asphyxia and TH on drug levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Prospective observational cohort study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Material and methods<\/jats:title>\n                  <jats:p>Term neonates with seizures of any cause were given phenobarbitone up to a maximum loading of 40\u2009mg\/kg followed by maintenance dose of 5\u2009mg\/kg\/day. Serum phenobarbitone levels were assessed after 4\u2009h of the initial loading dose and subsequently at 24, 48 and 72\u2009h from the time after maximum loading dose. Babies were divided into three groups Group 1 (HIE + TH\u2014hypoxic ischemic encephalopathy undergoing TH), Group 2 (HIE \u2212 TH\u2014hypoxic ischemic encephalopathy without TH) and Group 3 (non-HIE group).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 47 babies completed the study. Twenty-three (49%) received 20\u2009mg\/kg, 14 (30%) received 30\u2009mg\/kg and 10 (21%) received 40\u2009mg per kg of phenobarbitone as loading dose. HIE was the major cause of seizures 28 (59%) followed by hypoglycemia 7 (14%), cerebral malformations 4 (8%), inborn errors of metabolism 2 (4%) and hypocalcemia 1 (2%) while the cause of seizures was not known in 6 (13%). Median (IQR) Phenobarbitone levels at 72\u2009h in babies who received 20\u2009mg\/kg loading dose of phenobarbitone was 46.72 (44.02\u201350.49) mcg\/ml in HIE + TH group, 40.53 (28.66\u201365.09) mcg\/ml in HIE \u2212 TH group and 49 (37\u201365) mcg\/ml in non-HIE group. After a loading dose of 30\u2009mg\/kg, phenobarbitone level was 63.76 (59.5\u201365.94) mcg\/ml in HIE + TH group, 42.5 (34.75\u201348.75) mcg\/ml in HIE \u2212 TH group and 42.07 (40\u201349.05) mcg\/ml in non-HIE group. After 40\u2009mg\/kg loading dose, it was 62.3 (60.2\u201364.9) mcg\/ml in HIE + TH group, 57.0 (49.8\u201360.2) mcg\/ml in HIE \u2212 TH group and 48.15 (40.8\u201350.97) mcg\/ml in non-HIE group. In babies who received &amp;gt;20\u2009mg\/kg loading dose, 100% of HIE + TH, 80% of HIE \u2212 TH and 60% of non-HIE had supratherapeutic levels of phenobarbitone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>At higher loading doses of 30 and 40\u2009mg\/kg, steady state concentration of serum phenobarbitone is higher in babies with hypoxic ischemic encephalopathy who underwent TH than in babies with non-HIE causes of seizures. Loading dose beyond 20\u2009mg\/kg should be used with close monitoring of serum drug level<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/tropej\/fmac078","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T19:42:25Z","timestamp":1663962145000},"source":"Crossref","is-referenced-by-count":0,"title":["Comparing the effect of different loading doses of phenobarbitone on serum phenobarbitone levels in babies with neonatal seizures and effect of therapeutic hypothermia on phenobarbitone levels"],"prefix":"10.1093","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-2946","authenticated-orcid":false,"given":"Vinod","family":"Palaparthy","sequence":"first","affiliation":[{"name":"Department of Neonatology, Christian Medical College , Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3931-3536","authenticated-orcid":false,"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Christian Medical College , Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Rebekah","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Christian Medical College , Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niranjan","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Christian Medical College , Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"year":"2017","key":"2022092319273656900_fmac078-B1"},{"volume-title":"Cochrane Database of Systematic Reviews","year":"2007","author":"Evans","key":"2022092319273656900_fmac078-B2"},{"volume-title":"Neofax: A Manual of Drugs used in Neonatal Care","author":"Young","key":"2022092319273656900_fmac078-B3"},{"key":"2022092319273656900_fmac078-B4","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/MOP.0b013e328010c536","article-title":"Developmental factors regulating susceptibility to perinatal brain injury and seizures","volume":"18","author":"Jensen","year":"2006","journal-title":"Curr Opin Pediatr"},{"key":"2022092319273656900_fmac078-B5","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.clp.2009.08.001","article-title":"Neonatal seizures: an update on mechanisms and management","volume":"36","author":"Jensen","year":"2009","journal-title":"Clin Perinatol"},{"key":"2022092319273656900_fmac078-B6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s40265-016-0554-7","article-title":"Pharmacotherapy for neonatal seizures: current knowledge and future perspectives","volume":"76","author":"Donovan","year":"2016","journal-title":"Drugs"},{"key":"2022092319273656900_fmac078-B7","doi-asserted-by":"crossref","first-page":"F346","DOI":"10.1136\/archdischild-2015-309639","article-title":"Management and investigation of neonatal encephalopathy: 2017 update","volume":"102","author":"Martinello","year":"2017","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"2022092319273656900_fmac078-B8","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1542\/neo.13-4-e213","article-title":"Neonatal seizures","volume":"13","author":"Olson","year":"2012","journal-title":"Neoreviews"},{"key":"2022092319273656900_fmac078-B9","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1056\/NEJM199908123410704","article-title":"Phenobarbital compared with phenytoin for the treatment of neonatal seizures","volume":"341","author":"Painter","year":"1999","journal-title":"N Engl J Med"},{"year":"2021","key":"2022092319273656900_fmac078-B10"},{"key":"2022092319273656900_fmac078-B11"},{"key":"2022092319273656900_fmac078-B12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1046\/j.1365-2125.1998.00769.x","article-title":"Therapeutic drug monitoring\u2014antiepileptic drugs","volume":"46","author":"Eadie","year":"1998","journal-title":"Br J Clin Pharmacol"},{"key":"2022092319273656900_fmac078-B13","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/j.1528-1167.2011.02978.x","article-title":"Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia: phenobarbital and Therapeutic Hypothermia","volume":"52","author":"Filippi","year":"2011","journal-title":"Epilepsia"},{"key":"2022092319273656900_fmac078-B14","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s40262-012-0004-y","article-title":"Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach","volume":"51","author":"van den Broek","year":"2012","journal-title":"Clin Pharmacokinet"},{"key":"2022092319273656900_fmac078-B15","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1097\/PCC.0b013e31825bbbc2","article-title":"Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia","volume":"14","author":"Shellhaas","year":"2013","journal-title":"Pediatr Crit Care Med"}],"container-title":["Journal of Tropical Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/tropej\/article-pdf\/68\/5\/fmac078\/45985897\/fmac078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/tropej\/article-pdf\/68\/5\/fmac078\/45985897\/fmac078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T19:42:50Z","timestamp":1663962170000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/tropej\/article\/doi\/10.1093\/tropej\/fmac078\/6712682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,4]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/tropej\/fmac078","relation":{},"ISSN":["0142-6338","1465-3664"],"issn-type":[{"type":"print","value":"0142-6338"},{"type":"electronic","value":"1465-3664"}],"subject":[],"published-other":{"date-parts":[[2022,10,1]]},"published":{"date-parts":[[2022,8,4]]},"article-number":"fmac078"}}