Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy





Levetiracetam; Oxcarbazepine; Children with epilepsy; Multidrug resistance protein 1; Neuropeptide Y; Efficacy


The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.


Download data is not yet available.


Bossennec M, Di Roio A, Caux C, Ménétrier-Caux C. MDR1 in immunity: friend or foe? Oncoimmunology. 2018;7(12):e1499388.

Chen M, Hou C, Huo D, Bao J, Fa H, Shen C. An electrochemical DNA biosensor based on nitrogen-doped graphene/Au nanoparticles for human multidrug resistance gene detection. Biosens Bioelectron. 2016;85:684-91.

Chen W, Tan Y, Ge Y, Chen Y, Liu X. The effects of levetiracetam on cerebrospinal fluid and plasma NPY and GAL, and on the components of stress response system, hs-CRP, and S100B protein in serum of patients with refractory epilepsy. Cell Biochem Biophys. 2015;73(2):489-94.

Corder KM, Li Q, Cortes MA, Bartley AF, Davis TR, Dobrunz LE. Overexpression of neuropeptide Y decreases responsiveness to neuropeptide Y. Neuropeptides 2020;79: 101979.

Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21(8):904-19.

Ge T, Yang W, Fan J, Li B. Preclinical evidence of ghrelin as a therapeutic target in epilepsy. Oncotarget. 2017;8(35):59929.

Gujjar AR, Nandhagopal R, Jacob PC, Al-Hashim A, Al-Amrani K, Ganguly SS, et al. Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study. Seizure. 2017;49:8-12.

Koop JI, Loman MM. Neuropsychological assessment of infants, toddlers, and young children with epilepsy. J Pediatr Epilepsy. 2017;6(1):019-30.

Lin W-w, Li X-w, Jiao Z, Zhang J, Rao X, Zeng D-y, et al. Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric epilepsy patients and its application in individualised dosage regimens. Eur J Clin Pharmacol. 2019;75(3):381-92.

Loiacono G, Masci M, Zaccara G, Verrotti A. The treatment of neonatal seizures: focus on levetiracetam. J Matern Fetal Neonatal Med. 2016;29(1):69-74.

Moshé SL, Perucca E, Ryvlin P, Tomson T. Epilepsy: new advances. Lancet. 2015;385(9971):884-98.

Rodrigues C, Chiron C, Rey E, Dulac O, Comets E, Pons G, et al. Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children. Br J Clin Pharmacol. 2017;83(12):2695-708.

Schmidt DB, White S, Shukralla A, Castillo SM. Oxcarbazepine add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2016;11:CD002028. (link: https://pubmed.ncbi.nlm.nih.gov/10908522/).

» https://pubmed.ncbi.nlm.nih.gov/10908522/

Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393(10172):689-701.

Wang G-B, Long W, Li X-D, Xu G-Y, Lu J-X. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with positron emission tomography-computed tomography (PET-CT) and video-electroencephalography (VEEG) have excellent diagnostic value in preoperative localization of epileptic foci in children with epilepsy. Med Sci Monit. 2017;23:1-10.

Wang J, Liang C. Clinical effect and influence on congnitive reaction of single use of valproate, oxcarbazepine, and levetiracetam in treatment of children epilepsy. Drug Evaluation Research. 2017;40:687-90.

Weijenberg A, Brouwer OF, Callenbach PM. Levetiracetam monotherapy in children with epilepsy: a systematic review. CNS drugs. 2015;29(5):371-82.

Woldbye DPD, Gøtzsche CR, Klemp K, Berezin V, Bock E. Neuropeptide Y-derived peptides. 2018. https://www.patentsencyclopedia.com/app/20160060320

» https://www.patentsencyclopedia.com/app/20160060320

Yang T, Kong B, Kuang Y, Cheng L, Gu J, Zhang J, et al. Emodin plays an interventional role in epileptic rats via multidrug resistance gene 1 (MDR1). Int J Clin Exp Pathol. 2015;8(3):3418-3425.

Zhibin L, Jiang H, Xiao H. Efficacy and safety of oxcarbazepine combined with levetiracetam on children with epilepsy. The Journal of Practical Medicine. 2016;32: 2734-36.




How to Cite

Wang, J. (2023). Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy. Brazilian Journal of Pharmaceutical Sciences, 59, e21414. https://doi.org/10.1590/s2175-97902023e21414



Original Article