The effect of serum levetiracetam concentrations on therapeutic response and IL1-beta concentration in patients with epilepsy

被引:7
作者
Gulcebi, Medine I. [1 ]
Kendirli, Tansel [2 ]
Turgan, Zehra Asik [1 ]
Patsalos, Philip N. [3 ,4 ]
Onat, Filiz Yilmaz [1 ]
机构
[1] Univ Marmara, Sch Med, Dept Med Pharmacol, Istanbul, Turkey
[2] Univ Hlth Sci, Sch Med, Dept Neurol, Istanbul, Turkey
[3] NIHR Univ Coll London Hosp, UCL Inst Neurol, Dept Clin & Expt Epilepsy, Biomed Res Ctr, London, England
[4] Chalfont Ctr Epilepsy, Therapeut Drug Monitoring Unit, Gerrards Cross, England
关键词
Antiepileptic drugs; Seizure frequency; Adverse effect; Cytokine; ANTIEPILEPTIC DRUGS; ILAE-COMMISSION; CHILDREN; LAMOTRIGINE; EFFICACY;
D O I
10.1016/j.eplepsyres.2018.09.015
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Assessment of the relevance between serum drug concentration to its therapeutic response is a valid monitoring strategy for the clinical efficacy of antiepileptic drugs (AEDs). Levetiracetam (LEV) is a broad spectrum AED with a possible anti-inflammatory effect. We aimed to determine the relationship between LEV concentrations and its therapeutic response, and the effect of LEV on IL1-beta concentrations in patients with epilepsy. Methods: Patients on monotherapy (n = 7) or polytherapy (n = 15) with LEV for their seizures management were included. Blood samples of each patient were collected: just before LEV intake, 1 h, 2 h, 4 h and 8 h following the last dose. Serum LEV concentrations were measured by liquid chromatography mass spectrometry and IL1-beta concentrations by chemiluminescent immunometric assay. Concentration to dose (C/D) ratio values was used for analyses. LEV concentrations were compared between responders (<= 1 seizure/month) and non responders (> 1 seizure/month) and patients with or without adverse reactions. IL1-beta concentrations before and at 2 h following LEV ingestion were compared in order to detect the effect of the increase in serum LEV concentration on IL1-beta. Results: Although there was no change in LEV (C/D) ratio or LEV maximum concentration (Cmax)/D ratio of the responders and non-responders, the C/D ratio following 1 h of LEV intake (2.17 +/- 0.59 kg.day/L) and Cmax/D ratio (2.25 +/- 0.56 kg.day/L) in the patients with adverse effects was significantly higher than for the patients without adverse effects (1.09 +/- 0.12 kg.day/L and 1.49 +/- 0.14 kg.day/L respectively). A statistically significant decrease was found in the IL1-beta concentration to LEV (C/D) ratio with the increase in LEV concentration in patients on LEV monotherapy. Conclusion: The possible relationship between LEV Cmax and its therapeutic response or IL1-beta concentrations may be an importance indication of LEV antiepileptic efficacy. Consequently, monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects.
引用
收藏
页码:17 / 22
页数:6
相关论文
共 30 条
[1]  
Aldaz A, 2018, THER DRUG MONIT, V40, P130, DOI 10.1097/FTD.0000000000000470
[2]   Pharmacogenomics in epilepsy [J].
Balestrini, Simona ;
Sisodiya, Sanjay M. .
NEUROSCIENCE LETTERS, 2018, 667 :27-39
[3]   A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1β [J].
Balosso, Silvia ;
Maroso, Mattia ;
Sanchez-Alavez, Manuel ;
Ravizza, Teresa ;
Frasca, Angelisa ;
Bartfai, Tamas ;
Vezzani, Annamaria .
BRAIN, 2008, 131 :3256-3265
[4]   Levetiracetam in clinical practice: Long-term experience in patients with refractory epilepsy referred to a tertiary epilepsy center [J].
Bootsma, H. P. R. ;
Ricker, L. ;
Diepman, L. ;
Gehring, J. ;
Hulsman, J. ;
Lambrechts, D. ;
Leenen, L. ;
Majoie, M. ;
Schellekens, A. ;
de Krom, M. ;
Aldenkamp, A. P. .
EPILEPSY & BEHAVIOR, 2007, 10 (02) :296-303
[5]   Psychiatric and behavioral side effects of anti-epileptic drugs in adolescents and children with epilepsy [J].
Chen, B. ;
Detyniecki, K. ;
Choi, H. ;
Hirsch, L. ;
Katz, A. ;
Legge, A. ;
Wong, R. ;
Jiang, A. ;
Buchsbaum, R. ;
Farooque, P. .
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY, 2017, 21 (03) :441-449
[6]   Therapeutic drug monitoring - antiepileptic drugs [J].
Eadie, MJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1998, 46 (03) :185-193
[7]   Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans [J].
Guenther, Sabina ;
Bauer, Sebastian ;
Hagge, Mareike ;
Knake, Susanne ;
Olmes, David G. ;
Tackenberg, Bjoern ;
Rosenow, Felix ;
Hamer, Hajo M. .
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, 2014, 23 (08) :666-669
[8]   The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy [J].
Gulcebi, Medine Idrizoglu ;
Ozkaynakci, Aydan ;
Goren, Mehmet Zafer ;
Aker, Rezzan Gulhan ;
Ozkara, Cigdem ;
Onat, Filiz Yilmaz .
EPILEPSY RESEARCH, 2011, 95 (1-2) :1-8
[9]   Implications of antiinflammatory properties of the anticonvulsant drug levetiracetam in astrocytes [J].
Haghikia, Aiden ;
Ladage, Kerstin ;
Hinkerohe, Daniel ;
Vollmar, Patrick ;
Heupel, Katharina ;
Dermietzel, Rolf ;
Faustmann, Pedro M. .
JOURNAL OF NEUROSCIENCE RESEARCH, 2008, 86 (08) :1781-1788
[10]   Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3-and Anti-CD40-Stimulated Blood In Vitro [J].
Himmerich, Hubertus ;
Bartsch, Stefanie ;
Hamer, Hajo ;
Mergl, Roland ;
Schoenherr, Jeremias ;
Petersein, Charlotte ;
Munzer, Alexander ;
Kirkby, Kenneth Clifford ;
Bauer, Katrin ;
Sack, Ulrich .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2014, 2014