Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy

Hagemann, Anne; Klimpel, Dennis; Bien, Christian G.; Brandt, Christian; May, Theodor W.

doi:10.1111/epi.16500

Cited by 8 publications

(4 citation statements)

References 16 publications

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“…We present two patients with three recently approved ASMs during pregnancy, brivaracetam in both, and additionally lacosamide and perampanel in one, using multiple measurements in various matrixes. Routine use of TDM for these drugs demonstrates pronounced pharmacokinetic variability between patients [8][9][10]. Brivaracetam and lacosamide are partly metabolized through CYP2C19.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation

Landmark¹,

Rektorli²,

Burns³

et al. 2021

Epileptic Disorders

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We present pharmacokinetic data during pregnancy and lactation for brivaracetam, lacosamide and perampanel based on two case studies. Patient 1 used brivaracetam as monotherapy and gave birth to twins. Patient 2 used a combination of brivaracetam, lacosamide and perampanel. In both patients, serum drug concentrations were monitored throughout the pregnancies. Drug concentrations were also analysed in umbilical cord blood at birth, in serum from the offspring and in breastmilk after five days and 3-11 weeks. There were minor changes in concentration/dose-ratios for brivaracetam and lacosamide. The mean milk/serum ratios for brivaracetam and lacosamide were 0.71 and 0.83, respectively, five days and 3-5 weeks after delivery. The perampanel serum concentration increased by up to 80% in Patient 2 during the last part of gestation. The mean milk/serum-ratio for perampanel was 0.13, unchanged from five days to five weeks after delivery. Whereas serum concentrations of brivaracetam and lacosamide remained fairly stable throughout pregnancy, perampanel concentrations seemed to steadily increase towards the end. The distribution to milk was considerable for brivaracetam and lacosamide and low for perampanel. More studies on mother-infant pairs are warranted to confirm these results in larger groups.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation

Landmark¹,

Rektorli²,

Burns³

et al. 2021

Epileptic Disorders

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show abstract

“…Logarithmizing both sides of the equation results in a linear representation of the model: Based on the model shown above, we removed nonsignificant effects in a backward selection process. As in previous studies on ASM interactions, 9,10 we used generalized estimation equations (GEEs; working correlation matrix: unstructured, link function: log) 11 to estimate the parameters and their 95% confidence intervals for the logarithmized model. These models allow multiple samples from one patient to be considered.…”

Section: Methodsmentioning

confidence: 99%

Ethosuximide lowers lamotrigine serum concentrations: Evidence for a clinically relevant interaction

Hagemann,

Herting,

Klimpel

et al. 2024

Epilepsia

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We investigated the effect of comedication with ethosuximide (ESM) on lamotrigine (LTG) blood levels. Based on observations from clinical practice, we hypothesized that ESM reduces the LTG serum concentration. We additionally evaluated this effect in the presence of concomitant valproic acid (VPA). We retrospectively analyzed samples of inpatients from our department who had been treated with a combination of ESM and LTG between 2017 and 2021. We additionally used data on LTG serum concentrations from a previously published cohort from our center. Generalized estimation equations (GEEs) were used for statistical analyses. We included 523 samples from 209 patients. GEE analyses showed that LTG trough serum concentrations were significantly lower in samples with ESM comedication and significantly higher in samples with concomitant VPA. The effect of ESM was moderated by patients' age; in children and adolescents, LTG serum concentrations were 37% lower than in samples without ESM, whereas in adults, LTG serum concentrations were 14% lower. The effect we found in our data is relevant to daily clinical practice, if patients are not seizure‐free despite typical daily LTG dosage, or if they develop side effects during ESM withdrawal. It should be considered especially in children and adolescents.

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“…A similar interaction was observed for brivaracetam (BRV). Serum concentrations were significantly lower in patients with strong enzyme-inducing AEDs (CBZ, PHT, and/or PHB/PRM, −49%) [35]. LC-UV validated assay with on-line extraction with restricted access carbon nanotubes (RACNTs) was applied to determine PRM, PHB and CBZ.…”

Section: Primidonementioning

confidence: 99%

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

et al. 2020

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The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st–3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted.

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Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy

Cited by 8 publications

References 16 publications

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation

Ethosuximide lowers lamotrigine serum concentrations: Evidence for a clinically relevant interaction

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

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