Pharmacokinetic Variability of Sulthiame: The Impact of Age, Drug-Drug Interactions, and Biochemical Markers of Toxicity in Patients with Epilepsy.

Autor:	Heger K; Department of Pharmacy, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway., Kjeldstadli K; Section for Clinical Pharmacology, Department of Pharmacology, Oslo University Hospital, Oslo, Norway., Ring N; Section for Clinical Pharmacology, Department of Pharmacology, Oslo University Hospital, Oslo, Norway., Aaberg KM; The National Center for Epilepsy, Sandvika, Member of the ERN EpiCare, Oslo University Hospital, Oslo, Norway; and., Kjeldsen SF; Section for Clinical Pharmacology, The National Center for Epilepsy, Department of Pharmacology, Oslo University Hospital, Oslo, Norway., Burns ML; Section for Clinical Pharmacology, The National Center for Epilepsy, Department of Pharmacology, Oslo University Hospital, Oslo, Norway., Johannessen SI; The National Center for Epilepsy, Sandvika, Member of the ERN EpiCare, Oslo University Hospital, Oslo, Norway; and.; Section for Clinical Pharmacology, The National Center for Epilepsy, Department of Pharmacology, Oslo University Hospital, Oslo, Norway., Johannessen Landmark C; Department of Pharmacy, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.; The National Center for Epilepsy, Sandvika, Member of the ERN EpiCare, Oslo University Hospital, Oslo, Norway; and.; Section for Clinical Pharmacology, The National Center for Epilepsy, Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Therapeutic drug monitoring [Ther Drug Monit] 2024 Apr 01; Vol. 46 (2), pp. 237-245. Date of Electronic Publication: 2023 Dec 27.
DOI:	10.1097/FTD.0000000000001146
Abstrakt:	Purpose: Sulthiame is an antiseizure medication increasingly used for epilepsy. The aim of this study was to investigate the pharmacokinetic variability of sulthiame in children and adults with epilepsy with respect to age, comedication, dose, serum concentration, and biochemical markers of toxicity in a clinical setting. Method: Retrospective quantitative data from the therapeutic drug monitoring (TDM) database at the Section for Clinical Pharmacology, the National Center for Epilepsy, Norway (2015-2021), were used. Results: TDM data from 326 patients (127 female/199 male) were included [mean age, 11.4 (range 2-44) years; mean weight, 41 (range 14-109) kg]. Interindividual pharmacokinetic variability in the concentration/(dose/body weight) (C/(D/kg)) ratio was 16-fold; intraindividual variability was up to 8-fold (coefficient of variation = 10%-78%). Young children (younger than 6 years) had a significantly lower C/(D/kg) ratio than older age groups ( P < 0.05). Various comedications did not significantly affect the C/(D/kg) ratio, possibly owing to the small sample size. However, CYP2C19-mediated inhibition by sulthiame was indicated because patients using clobazam and sulthiame (n = 28) had a 3.5-fold higher N-desmethylclobazam C/(D/kg) ratio than those using neutral comedication (n = 45; P < 0.001). Patients with pH values below the adjusted normal range (7.32-7.42; n = 15) had a 33% higher sulthiame concentration than those with normal pH values (n = 22; P < 0.05). Blood gas measurements, especially pH, may serve as markers of toxicity and can be used in combination with clinical data when toxicity is suspected. Conclusions: This study revealed the extensive intraindividual and interindividual pharmacokinetic variability of sulthiame, with age as a contributing factor. Sulthiame has clinically relevant interactions with clobazam. The use of TDM and pH as a biochemical marker may contribute to individualized and safe sulthiame treatment. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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