{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T13:44:40Z","timestamp":1693662280299},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second\u2010line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses, particularly in young children. The Established Status Epilepticus Treatment Trial, a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine\u2010refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients aged \u22652 years who continued to seizure despite receiving adequate doses of benzodiazepines were randomly assigned to FOS, LEV, or VPA infused over 10 minutes. A sparse blood\u2010sampling approach was used, with up to 2 samples collected per patient within 2 hours following drug administration. The objective of this work was to report early drug exposure of PHT, LEV, and VPA and plasma protein binding of PHT and VPA. Twenty\u2010seven children with median (interquartile range) age of 4 (2.5\u20106.5) years were enrolled. The total plasma concentrations ranged from 69 to 151.3 \u03bcg\/mL for LEV, 11.3 to 26.7 \u03bcg\/mL for PHT and 126 to 223 \u03bcg\/mL for VPA. Free fraction ranged from 4% to 19% for PHT and 17% to 51% for VPA. This is the first report in young children of LEV concentrations with convulsive status epilepticus as well as VPA concentrations after a 40 mg\/kg dose. Several challenges limited patient enrollment and blood sampling. Additional studies with a larger sample size are required to evaluate the exposure\u2010response relationships in this emergent condition.<\/jats:p>","DOI":"10.1002\/jcph.1801","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T15:03:42Z","timestamp":1608303822000},"page":"763-768","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High\u2010Dose Intravenous Administration in Young Children With Benzodiazepine\u2010Refractory Status Epilepticus"],"prefix":"10.1002","volume":"61","author":[{"given":"Abhishek G.","family":"Sathe","sequence":"first","affiliation":[{"name":"Center for Orphan Drug Research College of Pharmacy University of Minnesota  Minneapolis Minnesota USA"},{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota  Minneapolis Minnesota 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