View in EDS HTML Full Text PDF Full Text

Exposure‐safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.

Saved in:
Bibliographic Details
Title: Exposure‐safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.
Authors: Gidal, B. E., Jacobson, M. P., Ben‐Menachem, E., Carreño, M., Blum, D., Soares‐da‐Silva, P., Falcão, A., Rocha, F., Moreira, J., Grinnell, T., Ludwig, E., Fiedler‐Kelly, J., Passarell, J., Sunkaraneni, S.
Source: Acta Neurologica Scandinavica. Sep2018, Vol. 138 Issue 3, p203-211. 9p.
Subjects: Pharmacokinetics, Anticonvulsants, Drug efficacy, Medication safety, Partial epilepsy, Drug interactions, Therapeutics
Abstract: Objectives: Eslicarbazepine acetate (ESL) is a once‐daily (QD) oral antiepileptic drug (AED) for focal‐onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. Methods: Eslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. Results: Eslicarbazepine PK was described by a one‐compartment model with linear absorption and elimination. The probability of a treatment‐emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. Conclusions: Pharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision‐making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions. [ABSTRACT FROM AUTHOR]
Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
Full text is not displayed to guests.
FullText Links:
  – Type: pdflink
Text:
  Availability: 1
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 131169927
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Exposure‐safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Gidal%2C+B%2E+E%2E%22">Gidal, B. E.</searchLink><br /><searchLink fieldCode="AR" term="%22Jacobson%2C+M%2E+P%2E%22">Jacobson, M. P.</searchLink><br /><searchLink fieldCode="AR" term="%22Ben‐Menachem%2C+E%2E%22">Ben‐Menachem, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Carreño%2C+M%2E%22">Carreño, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Blum%2C+D%2E%22">Blum, D.</searchLink><br /><searchLink fieldCode="AR" term="%22Soares‐da‐Silva%2C+P%2E%22">Soares‐da‐Silva, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Falcão%2C+A%2E%22">Falcão, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Rocha%2C+F%2E%22">Rocha, F.</searchLink><br /><searchLink fieldCode="AR" term="%22Moreira%2C+J%2E%22">Moreira, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Grinnell%2C+T%2E%22">Grinnell, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Ludwig%2C+E%2E%22">Ludwig, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Fiedler‐Kelly%2C+J%2E%22">Fiedler‐Kelly, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Passarell%2C+J%2E%22">Passarell, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Sunkaraneni%2C+S%2E%22">Sunkaraneni, S.</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Acta+Neurologica+Scandinavica%22">Acta Neurologica Scandinavica</searchLink>. Sep2018, Vol. 138 Issue 3, p203-211. 9p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Pharmacokinetics%22">Pharmacokinetics</searchLink><br /><searchLink fieldCode="DE" term="%22Anticonvulsants%22">Anticonvulsants</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+efficacy%22">Drug efficacy</searchLink><br /><searchLink fieldCode="DE" term="%22Medication+safety%22">Medication safety</searchLink><br /><searchLink fieldCode="DE" term="%22Partial+epilepsy%22">Partial epilepsy</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+interactions%22">Drug interactions</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objectives: Eslicarbazepine acetate (ESL) is a once‐daily (QD) oral antiepileptic drug (AED) for focal‐onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. Methods: Eslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. Results: Eslicarbazepine PK was described by a one‐compartment model with linear absorption and elimination. The probability of a treatment‐emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. Conclusions: Pharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision‐making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=131169927
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/ane.12950
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 9
        StartPage: 203
    Subjects:
      – SubjectFull: Pharmacokinetics
        Type: general
      – SubjectFull: Anticonvulsants
        Type: general
      – SubjectFull: Drug efficacy
        Type: general
      – SubjectFull: Medication safety
        Type: general
      – SubjectFull: Partial epilepsy
        Type: general
      – SubjectFull: Drug interactions
        Type: general
      – SubjectFull: Therapeutics
        Type: general
    Titles:
      – TitleFull: Exposure‐safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Gidal, B. E.
      – PersonEntity:
          Name:
            NameFull: Jacobson, M. P.
      – PersonEntity:
          Name:
            NameFull: Ben‐Menachem, E.
      – PersonEntity:
          Name:
            NameFull: Carreño, M.
      – PersonEntity:
          Name:
            NameFull: Blum, D.
      – PersonEntity:
          Name:
            NameFull: Soares‐da‐Silva, P.
      – PersonEntity:
          Name:
            NameFull: Falcão, A.
      – PersonEntity:
          Name:
            NameFull: Rocha, F.
      – PersonEntity:
          Name:
            NameFull: Moreira, J.
      – PersonEntity:
          Name:
            NameFull: Grinnell, T.
      – PersonEntity:
          Name:
            NameFull: Ludwig, E.
      – PersonEntity:
          Name:
            NameFull: Fiedler‐Kelly, J.
      – PersonEntity:
          Name:
            NameFull: Passarell, J.
      – PersonEntity:
          Name:
            NameFull: Sunkaraneni, S.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 09
              Text: Sep2018
              Type: published
              Y: 2018
          Identifiers:
            – Type: issn-print
              Value: 00016314
          Numbering:
            – Type: volume
              Value: 138
            – Type: issue
              Value: 3
          Titles:
            – TitleFull: Acta Neurologica Scandinavica
              Type: main
ResultId 1