Drug-drug and drug-food interactions in an infant with early-onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet
Sodium channel 2 subunit α (SCN2A) mutations cause difficult-to-treat early-onset epilepsy. Effective treatment includes high-dose phenytoin or carbamazepine ± ketogenic diet (KD). We describe an infant with early-onset SCN2A-epilepsy with subtherapeutic carbamazepine concentration during transition...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
02 March 2021
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| In: |
British journal of clinical pharmacology
Year: 2021, Volume: 87, Issue: 3, Pages: 1568-1573 |
| ISSN: | 1365-2125 |
| DOI: | 10.1111/bcp.14503 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1111/bcp.14503 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14503 
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| Author Notes: | Tatjana Welzel, Victoria C. Ziesenitz, Peter Weber, Alexandre N. Datta, Johannes N. van den Anker, Verena Gotta |
| Summary: | Sodium channel 2 subunit α (SCN2A) mutations cause difficult-to-treat early-onset epilepsy. Effective treatment includes high-dose phenytoin or carbamazepine ± ketogenic diet (KD). We describe an infant with early-onset SCN2A-epilepsy with subtherapeutic carbamazepine concentration during transition from phenytoin treatment to avoid long-term neurotoxicity. The transition from high-dose phenytoin (20 mg kg−1 d−1, concentration: ≥20 mg/L) with KD, to carbamazepine (50-75 mg kg−1 d−1, concentration: 9-12 mg/L) lasted 85 days, which we suspected was due to significant drug-drug and/or drug-food interactions. Model-based analysis of carbamazepine pharmacokinetics quantified significant time- and dose-dependent phenytoin-mediated CYP3A4 induction and carbamazepine concentration-dependent auto-induction (apparent clearance increased up to 2.5/3-fold). Lower carbamazepine concentrations under KD were modelled as decreased relative bioavailability (44%), potentially related to decreased fraction absorbed (unexpected for this lipophilic drug), increased intestinal/hepatic metabolism and/or decreased protein-binding with KD. This suggests importance of carbamazepine-concentration monitoring during KD-introduction/removal and necessity of high carbamazepine doses to achieve therapeutic concentrations, especially in infants treated with high-dose phenytoin. |
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| Item Description: | Gesehen am 24.04.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1365-2125 |
| DOI: | 10.1111/bcp.14503 |