Evidence map›Paper›PMID 33336359›Full record

Trial reportJournal of clinical pharmacology2021

Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High-Dose Intravenous Administration in Young Children With Benzodiazepine-Refractory Status Epilepticus.

Abhishek G Sathe, Usha Mishra, Vijay Ivaturi, Richard C Brundage, James C Cloyd, Jordan J Elm, James M Chamberlain, Robert Silbergleit, Jaideep Kapur, Daniel H Lowenstein and 5 more

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Levetiracetam Pharmacokinetics and Brain Uptake in a Lateral Fluid Percussion Injury Rat Model.The Journal of pharmacology and experimental therapeutics · 2023
    Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 11 institutions in 3 countries.

Abhishek G SatheCenter for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Usha MishraCenter for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Vijay IvaturiCenter for Translational Medicine, University of Maryland, Baltimore, Maryland, USA.
Richard C BrundageDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
James C CloydCenter for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Jordan J ElmDepartment of Public Health Science, Medical University of South Carolina, Charleston, South Carolina, USA.
James M ChamberlainDivision of Emergency Medicine, Children's National Hospital and the Department of Pediatrics and Emergency Medicine, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, USA.
Robert SilbergleitDepartment of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Jaideep KapurDepartment of Neurology and Department of Neuroscience, Brain Institute, University of Virginia, Charlottesville, Virginia, USA.
Daniel H LowensteinDepartment of Neurology, University of California, San Francisco, California, USA.
Shlomo ShinnarMontefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Hannah R CockClinical Neurosciences Academic Group, Institute of Molecular and Clinical Sciences, St George's University of London, London, UK.
Nathan B FountainDepartment of Neurology, Comprehensive Epilepsy Program, Charlottesville, Virginia, USA.
Lynn BabcockDepartment of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
Lisa D ColesCenter for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
University of Minnesota · USAllen Institute for Brain Science · USEpilepsy Foundation · AUGeorge Washington University Hospital · USMedical University of South Carolina · USMontefiore Medical Center · USSt George's, University of London · GBUniversity of California, San Francisco · USUniversity of Cincinnati · USUniversity of Maryland, Baltimore · USUniversity of Michigan–Ann Arbor · US

Funding

Neurologic Emergencies Treatment Trials Network: Clinical Coordinating CenterU01NS056975 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BARSAN, WILLIAM G · 2006 to 2015
$40.4M
Established Status Epilepticus Treatment Trial (ESETT)U01NS088034 · NINDS · UNIVERSITY OF VIRGINIA · PI CHAMBERLAIN, JAMES, KAPUR, JAIDEEP · 2014 to 2018
$16.3M
Neurological Emergencies Treatment Trials Network Statistical and Data ManagementU01NS059041 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DURKALSKI, VALERIE L, PALESCH, YUKO Y · 2006 to 2015
$9.1M
Established Status Epilepticus Treatment Trial (ESETT) - SDMCU01NS088023 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ELM, JORDAN J. · 2014 to 2018
$2.0M
ESETT Pharmacokinetic-Pharmacodynamic StudyR01NS099653 · NINDS · UNIVERSITY OF MINNESOTA · PI CLOYD, JAMES C., COLES, LISA D · 2017 to 2019
$1.0M
NINDS NIH HHS R01 NS099653NINDS NIH HHS U01 NS056975NINDS NIH HHS U01 NS059041NINDS NIH HHS U01 NS088023NINDS NIH HHS U01 NS088034
6 · The paper itself

Abstract

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line 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-refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients aged ≥2 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-sampling 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-seven children with median (interquartile range) age of 4 (2.5-6.5) years were enrolled. The total plasma concentrations ranged from 69 to 151.3 μg/mL for LEV, 11.3 to 26.7 μg/mL for PHT and 126 to 223 μg/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-response relationships in this emergent condition.

Indexed as

AnticonvulsantsBenzodiazepinesChildChild, PreschoolDose-Response Relationship, DrugFemaleHumansInfusions, IntravenousLevetiracetamMalePhenytoinProtein BindingStatus EpilepticusValproic AcidAnticonvulsantsBenzodiazepinesfosphenytoinLevetiracetamPhenytoinValproic Acidcentral nervous system (CNS)clinical pharmacology (CPH)clinical trials (CTR)emergency medicine (EME)exposure-responseneurology (NEU)pediatrics (PED)pharmacokinetics and drug metabolismprotein bindingsparse sampling

Identifiers

PMID33336359
PMCPMC8089035
OpenAlexW3116622638

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.