{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:19:08Z","timestamp":1753877948660,"version":"3.41.2"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,17]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets administered to neonates to terminate seizures.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A prospective, observational study of neonates admitted with seizures to Tygerberg Hospital. Participants received crushed levetiracetam (diluted in saline) given orally or via naso-\/orogastric tube. At steady-state, pharmacokinetic sampling was performed at pre-dose, 1.5, 2.5 and 4 h post-dose. Maximum concentration (Cmax), time to Cmax (Tmax), trough concentrations (Ctrough) and area under the concentration-time curve (AUC0\u201312) were calculated using non-compartmental analysis. Seizure termination and safety profiles were documented.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Nineteen participants were grouped into three dosing ranges: (i) 5\u201315\u2009mg\/kg\/12-hourly, (ii) 15\u201325\u2009mg\/kg\/12-hourly and (iii) 25\u201335\u2009mg\/kg\/12-hourly. Range 1 demonstrated AUC0\u201312 167.0\u2009\u00b1\u200945.6\u2009h*\u03bcg\/mL, Cmax 19.19\u2009\u00b1\u20094.12\u2009\u03bcg\/mL and Ctrough 9.99\u2009\u00b1\u20093.86\u2009\u00b5g\/mL. Range 2, AUC0\u201312 316.5\u2009\u00b1\u2009108.4\u2009h*\u03bcg\/mL, Cmax 35.12\u2009\u00b1\u200910.54\u2009\u00b5g\/mL and Ctrough 19.25\u2009\u00b1\u20098.48\u2009\u00b5g\/mL. Range 3, AUC0\u201312 290.9 (range 176.14\u2013405.59) h*\u03bcg\/mL, Cmax 36.11 (range 27.58\u201344.64) \u00b5g\/mL and Ctrough 13.03 (2.98\u201323.07) \u00b5g\/mL. Seizures terminated in 17\/19 (90%) neonates by day 3 and 19\/19 (100%) by day 4 post-levetiracetam initiation.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Crushed levetiracetam has comparable pharmacokinetics to historical data. No pharmacokinetic differences were observed between oral vs. naso-\/orogastric administration. Crushed levetiracetam tablets can be considered for neonates in low-resource settings where intravenous and syrup access is limited.<\/jats:p>\n <\/jats:sec>\n \n LAY SUMMARY<\/jats:title>\n Intravenous preparations of antiepileptic medications are used in the management of neonatal seizures. Various established standard of care intravenous antiepileptic medicines are unavailable nationally and internationally due to reasons outside our control. This stock shortage included intravenous phenobarbitone which is the first-line treatment for paediatric seizures. Due to phenobarbital shortage, levetiracetam has been identified by the neonatologists at Tygerberg Hospital, Cape Town, South Africa, as a suitable treatment option due to its efficacy and safety profile. However, intravenous levetiracetam and oral syrup is not registered in South Africa. Levetiracetam tablets are being crushed, dissolved and administered to neonates. There are no data available on the absorption of crushed levetiracetam tablets administered to neonates via a nasogastric tube. This study characterized the pharmacokinetic profile of crushed levetiracetam administered to neonates. We selected neonates receiving levetiracetam from the neonatal wards at Tygerberg hospital and drew blood to analyse the levetiracetam concentrations at 4 different time points. We found that the overall exposure of crushed levetiracetam tablets were comparable to the exposures achieved in historical data of the unaltered formulations. We concluded that crushed levetiracetam tablets can be considered for neonates in low resource settings where intravenous and syrup access is limited.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/tropej\/fmab041","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T12:37:30Z","timestamp":1619699850000},"source":"Crossref","is-referenced-by-count":1,"title":["The Pharmacokinetics of Crushed Levetiracetam Tablets Administered to Neonates"],"prefix":"10.1093","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-0320","authenticated-orcid":false,"given":"Veshni","family":"Pillay-Fuentes Lorente","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrie","family":"Bekker","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gugu T J","family":"Kali","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizel G","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma W","family":"Van der Merwe","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed A","family":"Abulfathi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa"},{"name":"Department of Clinical Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Medical Sciences, University of Maiduguri, Maiduguri 600004, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-5150","authenticated-orcid":false,"given":"Eric H","family":"Decloedt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South 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