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Levetiracetam Pharmacokinetics and Brain Uptake in a Lateral Fluid Percussion Injury Rat Model.
Coles, Lisa D; Saletti, Patricia G; Lisgaras, Christos Panagiotis; Casillas-Espinosa, Pablo M; Liu, Wei; Li, Qianyun; Jones, Nigel C; Shultz, Sandy; Ali, Idrish; Brady, Rhys; Yamakawa, Glenn; Hudson, Matt; Silva, Juliana; Braine, Emma; Mishra, Usha; Cloyd, James C; O'Brien, Terence J; Moshé, Solomon L; Galanopoulou, Aristea S.
Afiliação
  • Coles LD; University 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
  • Saletti PG; University 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
  • Lisgaras CP; University 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
  • Casillas-Espinosa PM; University 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
  • Liu W; University 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
  • Li Q; University 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
  • Jones NC; University 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
  • Shultz S; University 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
  • Ali I; University 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
  • Brady R; University 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
  • Yamakawa G; University 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
  • Hudson M; University 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
  • Silva J; University 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
  • Braine E; University 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
  • Mishra U; University 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
  • Cloyd JC; University 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
  • O'Brien TJ; University 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
  • Moshé SL; University 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
  • Galanopoulou AS; University 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
J Pharmacol Exp Ther ; 386(2): 259-265, 2023 08.
Article em En | MEDLINE | ID: mdl-37316328
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Epilepsia Pós-Traumática / Lesões Encefálicas Traumáticas Tipo de estudo: Guideline Limite: Animals Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Epilepsia Pós-Traumática / Lesões Encefálicas Traumáticas Tipo de estudo: Guideline Limite: Animals Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 2023 Tipo de documento: Article