Pharmacokinetics of eslicarbazepine acetate at steady-state in adults with partial-onset seizures

E. Perucca, C. Elger, P. Halász, A. Falcão, L. Almeida, P. Soares-da-Silva

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs). Methods: Blood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24. h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400. mg (n= 7), 800. mg (n= 26) or 1200. mg (n= 18) once-daily. Most patients (n= 29, 56.9%) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n= 34, 66.7%) and valproic acid (n= 19, 37.3%). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry. Results: Similarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (C max) 2h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20h in patients receiving ESL doses of 400, 800, and 1200mg once daily, respectively. Eslicarbazepine C max were 9.7, 15.5 and 23.0μg/mL, and areas under the plasma concentration-time curve over the dosing interval (AUC 0-24) were 132.5, 205.4 and 336.1μgh/mL in patients receiving ESL doses of 400, 800 and 1200mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (C max and AUC 0-24) were dose-proportional. R-licarbazepine and OXC were minor metabolites. Conclusions: Following once-daily oral administration of ESL 400. mg, 800. mg and 1200. mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalEpilepsy Research
Volume96
Issue number1-2
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Seizures
Pharmacokinetics
Anticonvulsants
Area Under Curve
eslicarbazepine acetate
Carbamazepine
Valproic Acid
Liquid Chromatography
Oral Administration
Half-Life
eslicarbazepine
Epilepsy
Mass Spectrometry
Healthy Volunteers

Keywords

  • Antiepileptic drugs
  • Eslicarbazepine acetate
  • Partial-onset seizures
  • Pharmacokinetics
  • Steady-state

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Pharmacokinetics of eslicarbazepine acetate at steady-state in adults with partial-onset seizures. / Perucca, E.; Elger, C.; Halász, P.; Falcão, A.; Almeida, L.; Soares-da-Silva, P.

In: Epilepsy Research, Vol. 96, No. 1-2, 09.2011, p. 132-139.

Research output: Contribution to journalArticle

Perucca, E. ; Elger, C. ; Halász, P. ; Falcão, A. ; Almeida, L. ; Soares-da-Silva, P. / Pharmacokinetics of eslicarbazepine acetate at steady-state in adults with partial-onset seizures. In: Epilepsy Research. 2011 ; Vol. 96, No. 1-2. pp. 132-139.
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abstract = "Objective: To evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs). Methods: Blood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24. h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400. mg (n= 7), 800. mg (n= 26) or 1200. mg (n= 18) once-daily. Most patients (n= 29, 56.9{\%}) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n= 34, 66.7{\%}) and valproic acid (n= 19, 37.3{\%}). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry. Results: Similarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (C max) 2h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20h in patients receiving ESL doses of 400, 800, and 1200mg once daily, respectively. Eslicarbazepine C max were 9.7, 15.5 and 23.0μg/mL, and areas under the plasma concentration-time curve over the dosing interval (AUC 0-24) were 132.5, 205.4 and 336.1μgh/mL in patients receiving ESL doses of 400, 800 and 1200mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (C max and AUC 0-24) were dose-proportional. R-licarbazepine and OXC were minor metabolites. Conclusions: Following once-daily oral administration of ESL 400. mg, 800. mg and 1200. mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.",
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T1 - Pharmacokinetics of eslicarbazepine acetate at steady-state in adults with partial-onset seizures

AU - Perucca, E.

AU - Elger, C.

AU - Halász, P.

AU - Falcão, A.

AU - Almeida, L.

AU - Soares-da-Silva, P.

PY - 2011/9

Y1 - 2011/9

N2 - Objective: To evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs). Methods: Blood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24. h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400. mg (n= 7), 800. mg (n= 26) or 1200. mg (n= 18) once-daily. Most patients (n= 29, 56.9%) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n= 34, 66.7%) and valproic acid (n= 19, 37.3%). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry. Results: Similarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (C max) 2h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20h in patients receiving ESL doses of 400, 800, and 1200mg once daily, respectively. Eslicarbazepine C max were 9.7, 15.5 and 23.0μg/mL, and areas under the plasma concentration-time curve over the dosing interval (AUC 0-24) were 132.5, 205.4 and 336.1μgh/mL in patients receiving ESL doses of 400, 800 and 1200mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (C max and AUC 0-24) were dose-proportional. R-licarbazepine and OXC were minor metabolites. Conclusions: Following once-daily oral administration of ESL 400. mg, 800. mg and 1200. mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.

AB - Objective: To evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs). Methods: Blood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24. h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400. mg (n= 7), 800. mg (n= 26) or 1200. mg (n= 18) once-daily. Most patients (n= 29, 56.9%) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n= 34, 66.7%) and valproic acid (n= 19, 37.3%). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry. Results: Similarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (C max) 2h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20h in patients receiving ESL doses of 400, 800, and 1200mg once daily, respectively. Eslicarbazepine C max were 9.7, 15.5 and 23.0μg/mL, and areas under the plasma concentration-time curve over the dosing interval (AUC 0-24) were 132.5, 205.4 and 336.1μgh/mL in patients receiving ESL doses of 400, 800 and 1200mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (C max and AUC 0-24) were dose-proportional. R-licarbazepine and OXC were minor metabolites. Conclusions: Following once-daily oral administration of ESL 400. mg, 800. mg and 1200. mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.

KW - Antiepileptic drugs

KW - Eslicarbazepine acetate

KW - Partial-onset seizures

KW - Pharmacokinetics

KW - Steady-state

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