Pharmacokinetic interaction between modified Atkins diet and antiepileptic drugs in adults with drug-resistant epilepsy.
adults
antiepileptic drugs
epilepsy
ketogenic diet
ketosis
serum concentration
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
14
03
2019
revised:
12
09
2019
accepted:
15
09
2019
pubmed:
12
10
2019
medline:
16
4
2020
entrez:
12
10
2019
Statut:
ppublish
Résumé
The aim was to examine the influence of modified Atkins diet on serum concentration of antiepileptic drugs (AEDs). Prospective data from 63 adult patients with either focal or generalized drug-resistant epilepsy recruited to 12-week dietary treatment as add-on to AEDs are analyzed. AED serum concentrations, ketones, glucose, and hemoglobin A1c were measured before and after the dietary intervention. Paired t test was used and Spearman correlation coefficient, r, was estimated. Mean age was 37 years (range 16-65 years). Mean serum concentrations of carbamazepine, clobazam, and valproate were significantly reduced after 4 and 12 weeks of the diet period (<.001 ≤ P ≤ .02). Levels of lacosamide, lamotrigine, and topiramate were less reduced (.02 ≤ P ≤ .08), whereas the serum concentrations of oxcarbazepine, zonisamide, and levetiracetam were unchanged (.06 ≤ P ≤ .90). The largest reduction in serum concentration was found for clobazam: mean reduction after 12 weeks was 1.5 μmol/L (34%). Percent change in serum concentration after 4 and 12 weeks of all drugs analyzed was -10.5% (95% confidence interval [CI] -14.1 to -6.8; n = 60; P < .001) and -13.5% (95% CI -18.8 to -8.3; n = 56; P < .001), respectively. Percent change in serum concentration of AEDs was not significantly correlated to percent change in seizure frequency after 12 weeks of dietary treatment (r = .14, P = .33, n = 53) but negatively correlated to urine ketosis (r = -.43; P = .003; n = 46). A reduction in AED serum concentrations may counteract a seizure-reducing effect of the diet, and in patients without such an effect, it may cause seizure aggravation. Thus, we recommend that clinicians who are treating patients with ketogenic diets monitor serum concentrations of the concomitant AEDs.
Substances chimiques
Anticonvulsants
0
Banques de données
GENBANK
['NCT01311440']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2235-2244Informations de copyright
© 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
Références
Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008;7:500-6.
Klein P, Tyrlikova I, Mathews GC. Dietary treatment in adults with refractory epilepsy: a review. Neurology. 2014;83:1978-85.
Kverneland M, Molteberg E, Iversen PO, Veierød MB, Taubøll E, Selmer KK, et al. Effect of modified Atkins diet in adults with drug-resistant focal epilepsy: a randomized clinical trial. Epilepsia. 2018;59:1567-76.
Kverneland M, Tauboll E, Selmer KK, Iversen PO, Nakken KO. Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Acta Neurol Scand. 2015;131:187-90.
Kverneland M, Selmer KK, Nakken KO, Iversen PO, Taubøll E. A prospective study of the modified Atkins diet for adults with idiopathic generalized epilepsy. Epilepsy Behav. 2015;53:197-201.
Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512-21.
Kossoff EH, Rowley H, Sinha SR, Vining EP. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia. 2008;49:316-9.
Norwegian Food Composition Database 2018. Norwegian Food Safety Authority, The Norwegian Directorate of Health, University of Oslo, 2011-17.Available at: www.matvaretabellen.no.
Sidhu S, Malhotra S, Garg SK. Influence of high fat diet (butter) on pharmacokinetics of phenytoin and carbamazepine. Methods Find Exp Clin Pharmacol. 2004;26:634-8.
Yu HY, Shen YZ. Pharmacokinetics of valproic acid in guinea-pigs with biliary abnormality. J Pharm Pharmacol. 1991;43:470-4.
Ahn JE, Bathena SPR, Brundage RC, Conway JM, Leppik IE, Birnbaum AK. Iron supplements in nursing home patients associated with reduced carbamazepine absorption. Epilepsy Res. 2018;147:115-8.
Heo G, Kim SH, Chang MJ. Effect of ketogenic diet and other dietary therapies on anti-epileptic drug concentrations in patients with epilepsy. J Clin Pharm Ther. 2017;42:758-64.
Johannessen Landmark C, Johannessen SI, Tomson T. Host factors affecting antiepileptic drug delivery-pharmacokinetic variability. Adv Drug Deliv Rev. 2012;64:896-910.
Pfeifer HH, Lyczkowski DA, Thiele EA. Low glycemic index treatment: implementation and new insights into efficacy. Epilepsia. 2008;49(Suppl 8):42-5.
Dahlin MG, Beck OM, Amark PE. Plasma levels of antiepileptic drugs in children on the ketogenic diet. Pediatr Neurol. 2006;35:6-10.
Coppola G, Verrotti A, D'Aniello A, Arcieri S, Operto FF, Della Corte R, et al. Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet. Acta Neurol Scand. 2010;122:303-7.