Bedeutung der Serumkonzentrationen von Antikonvulsiva

Steinhoff, Bernhard J.; Fröscher, W.

doi:10.1007/s10309-010-0148-4

Cited by 11 publications

(3 citation statements)

References 17 publications

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“…Especially with first-and second-generation ASMs such phenobarbital, phenytoin, and carbamazepine, socalled therapeutic ranges have been defined and are still widely used [26]. The definition of a therapeutic or reference range is a drug-specific span between upper and lower limits that defines the range of doses resulting in probable antiseizure efficacy without dose-related AEs [29]. The concept of such a general definition has been questioned.…”

Section: Discussionmentioning

confidence: 99%

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Steinhoff,

Georgiou,

Dietmann

et al. 2024

JCM

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Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Methods: Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Results: Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg–400 mg) and the plasma levels (3.8 mg/L–54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Conclusions: To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined.

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Section: Discussionmentioning

confidence: 99%

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Steinhoff,

Georgiou,

Dietmann

et al. 2024

JCM

View full text Add to dashboard Cite

show abstract

“…Especially with first-and second-generation ASMs such phenobarbital, phenytoin, and carbamazepine, so-called therapeutic ranges have been defined and are still widely used [28]. The definition of a therapeutic or reference range is a drug-specific span between upper and lower limits that defines the range of doses resulting in probable antiseizure efficacy without dose-related adverse events [31]. The concept of such a general definition has been questioned.…”

Section: Discussionmentioning

confidence: 99%

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability

Steinhoff,

Georgiou,

Dietmann

et al. 2024

Preprint

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Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) who suffer from ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies have suggested a high efficacy with unusually high seizure-free rates. We sought to investigate the serum trough levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. We analyzed samples from 101 PWEs treated with adjunct cenobamate under steady-state conditions. In all, 36 PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. We found a linear correlation between the daily doses (range: 100 mg – 400 mg) and the plasma levels (3.8 mg/l – 54.6 mg/l). Neither the daily doses nor the plasma levels differed significantly between seizure-free and non-responding PWEs or between PWEs with a satisfactory tolerability and those who experienced adverse events. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Still, to evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful.

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“…Die Indikation zur Bestimmung der Antiepileptikaserumkonzentrationen wird in einer gesonderten Übersicht [87] in diesem Heft dargestellt.…”

Section: Serumkonzentration Der Antiepileptikaunclassified

Laboratory monitoring in the pharmacotherapy of epilepsy

Fröscher

Steinhoff

2011

Z. Epileptol.

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Bedeutung der Serumkonzentrationen von Antikonvulsiva

Cited by 11 publications

References 17 publications

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability

Laboratory monitoring in the pharmacotherapy of epilepsy

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