Evidence map›Paper›PMID 37316328›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2023

Levetiracetam Pharmacokinetics and Brain Uptake in a Lateral Fluid Percussion Injury Rat Model.

Lisa D Coles, Patricia G Saletti, Christos Panagiotis Lisgaras, Pablo M Casillas-Espinosa, Wei Liu, Qianyun Li, Nigel C Jones, Sandy Shultz, Idrish Ali, Rhys Brady and 10 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
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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

20 authors at 5 institutions in 2 countries.

Lisa D ColesUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.) durh0016@umn.edu.
Patricia G SalettiUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Christos Panagiotis LisgarasUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Pablo M Casillas-EspinosaUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Wei LiuUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Qianyun LiUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Nigel C JonesUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Sandy ShultzUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Idrish AliUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Rhys BradyUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Glenn YamakawaUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Matt HudsonUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Juliana SilvaUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Emma BraineUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Usha MishraUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
James C CloydUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Terence J O'BrienUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Solomon L MoshéUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).
Aristea S GalanopoulouUniversity of Minnesota Twin Cities, Minneapolis, Minnesota (L.D.C., U.M., J.C.C.); Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy (P.G.S., C.P.L., W.L., Q.L., S.L.M., A.S.G.), Isabelle Rapin Division of Child Neurology (S.L.M., A.S.G.), Dominick P. Purpura Department of Neuroscience (S.L.M., A.S.G.), and Department of Pediatrics (S.L.M.), Albert Einstein College of Medicine, Bronx, New York; Department of Neuroscience, Monash University, Melbourne, Australia (P.M.C.-E., S.S., R.B., G.Y., M.H., J.S., E.B., T.J.O.); and The University of Melbourne, Parkville, Australia (R.B., G.Y., M.H., J.S., E.B., T.J.O.).ORCID 0000-0002-0472-2903
EpiBioS4Rx Study Group
Land Stewardship Project · USAlbert Einstein College of Medicine · USUniversity of Minnesota · USMonash University · AUUniversity of Minnesota System · US

Funding

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Public Engagement CoreU54NS100064 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ENGEL, JEROME NONE, GALANOPOULOU, ARISTEA S · 2017 to 2021
$21.7M
Consequences of Prolonged Febrile Seizures in ChildhoodR01NS043209 · NINDS · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI SHINNAR, SHLOMO · 2003 to 2012
$21.5M
Consequences of Prolonged Febrile Seizures in ChildhoodR37NS043209 · NINDS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI SHINNAR, SHLOMO · 2013 to 2019
$11.4M
Support for the Rose F. Kennedy IDDRCU54HD090260 · NICHD · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI WALKLEY, STEVEN UPSHAW · 2016 to 2020
$6.0M
GABA-inflammation interplay in infantile spasmsR01NS091170 · NINDS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI GALANOPOULOU, ARISTEA S · 2015 to 2020
$1.9M
NICHD NIH HHS U54 HD090260NINDS NIH HHS R01 NS043209NINDS NIH HHS R01 NS091170NINDS NIH HHS R37 NS043209NINDS NIH HHS U54 NS100064
6 · The paper itself

Abstract

Post-traumatic epilepsy (PTE) occurs in some patients after moderate/severe traumatic brain injury (TBI). Although there are no approved therapies to prevent epileptogenesis, levetiracetam (LEV) is commonly given for seizure prophylaxis due to its good safety profile. This led us to study LEV as part of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Project. The objective of this work is to characterize the pharmacokinetics (PK) and brain uptake of LEV in naïve control rats and in the lateral fluid percussion injury (LFPI) rat model of TBI after either single intraperitoneal doses or a loading dose followed by a 7-day subcutaneous infusion. Sprague-Dawley rats were used as controls and for the LFPI model induced at the left parietal region using injury parameters optimized for moderate/severe TBI. Naïve and LFPI rats received either a bolus injection (intraperitoneal) or a bolus injection followed by subcutaneous infusion over 7 days. Blood and parietal cortical samples were collected at specified time points throughout the study. LEV concentrations in plasma and brain were measured using validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods. Noncompartmental analysis and a naive-pooled compartmental PK modeling approach were used. Brain-to-plasma ratios ranged from 0.54 to 1.4 to 1. LEV concentrations were well fit by one-compartment, first-order absorption PK models with a clearance of 112 ml/h per kg and volume of distribution of 293 ml/kg. The single-dose pharmacokinetic data were used to guide dose selection for the longer-term studies, and target drug exposures were confirmed. Obtaining LEV PK information early in the screening phase allowed us to guide optimal treatment protocols in EpiBioS4Rx. SIGNIFICANCE STATEMENT: The characterization of levetiracetam pharmacokinetics and brain uptake in an animal model of post-traumatic epilepsy is essential to identify target concentrations and guide optimal treatment for future studies.

Indexed as

Brain Injuries, TraumaticEpilepsy, Post-TraumaticAnimalsAnticonvulsantsBrainDisease Models, AnimalLevetiracetamPercussionRatsRats, Sprague-DawleyTandem Mass SpectrometryAnticonvulsantsLevetiracetam

Identifiers

PMID37316328
PMCPMC10353071
OpenAlexW4380591046

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