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Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy
Author(s) -
Hagemann Anne,
Klimpel Dennis,
Bien Christian G.,
Brandt Christian,
May Theodor W.
Publication year - 2020
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16500
Subject(s) - primidone , carbamazepine , oxcarbazepine , medicine , phenytoin , epilepsy , concomitant , phenobarbital , pharmacokinetics , therapeutic drug monitoring , pharmacology , anesthesia , psychiatry
The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368 routinely collected blood samples from 148 inpatients from Mara Hospital (Bethel Epilepsy Center) and von Bodelschwingh Foundation Bethel were retrospectively evaluated. Generalized estimation equations (GEEs) were used for statistical analysis. GEE analyses showed that BRV trough serum concentrations were significantly lower in patients with strong enzyme‐inducing AEDs (carbamazepine, phenytoin, and/or phenobarbital/primidone, −49%), but were not affected by concomitant intake of oxcarbazepine or eslicarbazepine. Age and gender did not have a significant effect. An alternative GEE model analyzing the BRV level‐to‐dose ratios yielded comparable results. Our results from routine therapeutic drug monitoring data indicate that the effect of enzyme‐inducing AEDs on BRV serum concentrations is stronger than the 20%‐30% reduction in BRV exposure previously reported in pharmacokinetics studies. Further research is necessary to evaluate these differences and to elucidate possible clinical consequences.