Levetiracetam – epilepsy treatment, pharmacokinetics, mechanism of action, interaction and toxicity

Piotr Kozłowski, Wioleta Czępińska-Ćwik, Magdalena Kozłowska, Karolina Kozłowska

Abstract


Kozłowski Piotr, Czępińska-Ćwik Wioleta, Kozłowska Magdalena, Kozłowska Karolina. Levetiracetam – epilepsy treatment, pharmacokinetics, mechanism of action, interaction and toxicity. Journal of Education, Health and Sport. 2015;5(4):143-150. ISSN 2391-8306. DOI: 10.5281/zenodo.16694

http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%284%29%3A143-150

https://pbn.nauka.gov.pl/works/553762

http://dx.doi.org/10.5281/zenodo.16694

Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive

 

Deklaracja.

Specyfika i zawartość merytoryczna czasopisma nie ulega zmianie.

Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., że w roku 2014 nie będzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktów co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r.

The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014).

© The Author (s) 2015;

This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,

provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License

(http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.

This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial

use, distribution and reproduction in any medium, provided the work is properly cited.

The authors declare that there is no conflict of interests regarding the publication of this paper.

Received: 20.01.2015. Revised 27.03.2015. Accepted: 27.03.2015.

 

LEVETIRACETAM – EPILEPSY TREATMENT, PHARMACOKINETICS, MECHANISM OF ACTION, INTERACTION AND TOXICITY

 

Piotr Kozłowski1, Wioleta Czępińska-Ćwik2, Magdalena Kozłowska3, Karolina Kozłowska4

 

1 Katedra i Zakład Anatomii Prawidłowej Człowieka, UM w Lublinie

Klinika Chorób Wewnętrznych, 1 Wojskowy Szpital Kliniczny z Polikliniką w Lublinie

3 Katedra i Zakład Farmakologii doświadczalnej i Klinicznej, UM w Lublinie

4 Instytut Filologii Angielskiej, KUL

 

Uniwersytet Medyczny w Lublinie

ul. W. Chodźki 1, 20-093 Lublin

e-mail: piotr7176@gmail.com

 

Abstract

 

Epilepsy is a common chronic neurological disorder that requires a long-term antiepileptic drug therapy. Epilepsy affects approximately 1% of the world’s population, so about 50 million people worldwide have epilepsy. It more likely occurs among children and people over the age of 65. This chronic condition is characterized by recurrent, unprovoked epileptic seizures. Although there are many innovative methods of seizure control, such as neurosurgery, vagal nerve stimulations (VNS) and ketogenic diet, pharmacology is most forceful method of epilepsy treatment. Unfortunately, anticonvulsant drugs are not always effective; the number of non-responding patients is higher than 30% [2,25,29,31].

            Levetiracetam (LEV) is one of the newest AEDs, marketed worldwide only since 2000 [29]. This novel antiepileptic drug has a unique and non-standard mechanism of action. The structure of LEV is similar to the prototypical nootropic drug piracetam. Its novel mechanism of action is connected with the synaptic vesicle protein SV2A in the brain. The elimination plasma half-live of LEV is approximately from 6 to 8 hours among adults. About 66% of the drug is excreted unchanged and 27% as inactive hydrolysis product [12]. LEV is mainly removed by the kidneys so that elimination parallels kidney function (renal clearance: 0,6 ml/min/kg) [3,12,32]. LEV was found to be well tolerated and effective in all types of seizures in adults and children [18]. It can be also used in combinations with other AEDs. The drug may also be useful in treatment of Lennox-Gastaut syndrome [9].

            This article reviews available published data on LEV in the treatment of adults and children, including information about LEV`s pharmacokinetics, chemistry, mechanism of action, interactions and toxicity.

 

Key words: levetiracetam, antiepileptic drugs, seizures, epilepsy.


Keywords


levetiracetam, antiepileptic drugs, seizures, epilepsy.

Full Text:

PDF

References


Abou-Khalil B: Levetiracetam in the treatment of epilepsy. Pediatric epilepsy: diagnosis and treatment. Neuropsychiatr Dis Treat. 2008, 4 (3), 507-523.

Aronson JK: Side effects of drugs annual 26, 2003.

Bialer M: The pharmacokinetics and interactions of new antiepileptic drugs: an overview. The Drug Monit, 2005, 27(6), 722-26.

Bjorklund R: Health Alert. Epilepsy, 2006

Doheny HC, Whittington MA, Jefferys JGR, Patsalos PN: A comparison of the efficacy of carbamazepine and the novel antiepileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy. Br J Pharmacol, 2002, 135, 1425-1434.

Engel J, Pedley TA, Aicardi J, Dichter MA : Epilepsy: a comprehensive textbook volume 1, 2007, 1583-1592.

French J, Edrich P, Cramer JA: A systematic review of the safety profile of levetiracetam: a new antiepileptic drug. Epilepsy Res, 2001, 47,77-90.

French J: Use of levetiracetam in special populations. Epilepsia, 2001, 42 (Suppl.), 4,40-3.

Gambardella A, Labate A, Colosimo E, Ambrosio R, Quattrone A : Monotherapy for partial epilepsy: focus on levetiracetam. Neuropsychiatr Dis Treat. 2008, 4 (1), 33-38.

Gidal BE, Baltes E, Otoul C, Perucca E : Effect od levetiracetam on the pharmacokinetics of adjunetive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. Epilepsy Res, 2005, 64, 1-11.

Glauser TA, Pellock JM, Bebin EM, Fountain NB, Ritter FJ, Jensen CM, Shields WD: Efficacy and safety of levetiracetam in children with partial seizures: an open label trial. Epilepsia, 2002, 43 (5), 518-524.

Greiner –Sasanko E, Giannoutsos S, Lower DR, Virij MA, Krasowski MD : Drug monitoring: simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydrocarbazepine, and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam. NIH Public Access, J Chromatogr, 2007, 45(9), 616-622.

Hirsch LJ, Arif H, Buchsbaum R, Weintraub D, Lee J, Chang JT, Resor Jr SR, Bazil CW: Effect of age and comedication on levetiracetam pharmacokinetics and tolerability. Epilepsia, 2007, 48,1351-9.

Hunt S, Craig J, Russel A, Guthrie E, Parsons L, Robertson I, Waddell R, Irwin B et al.: Leveitiracetam in pragnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology, 2006, 67, 1876-9.

Katzung BG: Basic and clinical pharmacology. 2007, 383-384.

Keppra. Prescribing information. 2006.

Klitgaard H, Matagne A, Gobert J, Wülfert E : Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur J of Pharmacol, 1998, 353, 191-206.

Leppik IE: The place of levetiracetam in the treamtent of epilepsy. Epilepsia, 2001(Suppl. 4), S44-S45.

Levy RH: Antiepileptic drugs. 2002, 428-448.

Lukyanetz EA, Shkryl VM, Kostyuk PG: Selective blockade of N-type calcium channels by levetiracetam. Epilepsia, 2002, 43, 9-18.

Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalich SM, Matagne A, Fuks B : The synaptic vesicle protein SV2A is the binding site for the antepileptic drug levetiracetam. The National Academy of Sciences, 2004, 9861–9866.

Łuszczki JJ, Andres MM, Czuczwar P, Cioczek-Czuczwar A, Wojcik-Cwikla J, Ratnaraj N, Patsalos P, Czuczwar S: Levetiracetam potentiates the acute neurotoxic effects of topiramate and carbamazepine in rotarod test in mice. Eur Neuropharmacol, 2005, 15, 609-616.

Łuszczki JJ, Andres-Mach MM, Ratnaraj, Patsalos PN, Czuczwar SJ : Levetiracetam and felbamate interact bots pharmacodynamically and pharmacokinetically: an isobolographic analysis in the mouse maximal electroshock model. Epilepsia, 2007, 48 (4),806 –815.

Mandelbaum DE, Bunch M, Kuler SL, Venkatasubramanian A, Wollack JB: Efficacy of levetiracetam at 12 months in children classified by seizure type, cognitive status and previos anticonvulsant drug use. J Child Neurol, 2005, 20, 7.

Mazarti AM, Baldwin R, Klitgaard H, Matagne A, Wasterlain CG : Anticonvulsant effects of levetiracetam and levetiracetam – diazepam combinations in experimental status epilepticus. Epilepsy Res. 2004, 58 (2-3), 167-174.

Mazayani A, Raymon LP: Handbook of drug interactions: a clinical and forensic guide, 2004.

Package insert: Keppra. UCB Pharma, Smyrna, GA, 2002.

Patsalos PN, Duncan JS: Antilepileptic drugs. A review of clinically significant drug interactions. Drug Saf, 1993, 9, 156-184.

Patsalos PN: Pharmacokinetics profile of leveitracetam: toward ideal characteristics. Pharmacol Ther 2000, 85 (2),77-85.

Pellock JM, Dodson WE, Bourgeois FD: Pediatric epilepsy: diagnosis and treatment. 2008, 611-620.

Privitera MD, Ficker DM, Welty TE: Clinian`s guide to antiepileptic drug use. 2006, 65-71.

Radtke RA: Pharmacokinetics of levetiracetam. Epilepsia, 2001 (Suppl.), 42, 24-27.

Ramsay RE: Neurobiology of epilepsy and aging. 2007, 97.

Rho JM, Sankor R, Cavazos JE: Epilepsy: scientific foundations of clinical practices, 2004.

Rigo JM, Hans G, Nguyen L, Rocher V, Belachew S, Malgrange B, Leprince P, Moonen et al.: The antiepileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol, 2002, 136, 659-672.

Simon D, Fish D: The treatment of epilepsy, 2004, 443-450.

Simon D, Shorron: Handbook of epilepsy treatment. 2005, 144-145.

Sisodiya SM, Sander JW, Patsalos PN: carbamazepine toxicity during combination therapy with levetiracetam: a pharmacodynamic interaction. Epilepsy Res, 2002, 48, 217-219.

Strolin MB, Coupez R, Whomsley R, Nicolas JM, Collart P, Baltes E : Comparative pharmacokinetics and metabolism of levetiracetam, a new antu-epileptic agent, in mouse, rat, rabbit and dog. Xenobiotica, 2004, 34, 281-300.

Trojnar MK, Wojtal K, Trojnar MP, Czuczwar SJ : Stripentol. A novel antiepiletic drug. Pharmacol Rep, 2005, 57, 154-160.

Wheless JW: Levetiracetam in the treatment of childhood epilepsy. Neuropsychiar Dis Treat, 2007, 3 (4), 409- 421.

Wilner AN: Epilepsy – a doctor responds to his patients questions, 199 answers. 2003, 1-2.

Zhao Q, Jiang J, Li X, Lu ZS, Hu P : Single-dose pharmacokinetics of levetiracetam in healthy Chinese male subject. Br J Clin Pharmacol, 2006, 63,5, 614-615.


Refbacks

  • There are currently no refbacks.




Copyright (c)



Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

https://pbn.nauka.gov.pl/sedno-webapp/search?search&searchCategory=WORK&filter.inJournal=36616

POL-index 2011 - 2014

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-32a319c5-a850-4f44-ba70-1418a6087655

BASE 2011 - 2014

https://www.base-search.net/Search/Results?lookfor=Journal+of+Health+Sciences+%28Radom%29&type=all&oaboost=1&ling=1&name=&thes=&refid=dcrespl&newsearch=1

http://elibrary.ru/contents.asp?titleid=37467

http://journal.rsw.edu.pl/index.php/JHS/issue/archive

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

https://www.ncbi.nlm.nih.gov/nlmcatalog/101679844

Find a library that holds this journal: http://worldcat.org/issn/23918306

Journal Language(s): English 

PBN Poland

https://pbn.nauka.gov.pl/sedno-webapp/journals/49068

POL-index

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-c39c8169-88d2-45db-9e7f-d948ce9981c4

BASE

https://www.base-search.net/Search/Results?join=AND&bool0[]=AND&lookfor0[]=2391-8306&type0[]=all&page=11&l=pl&oaboost=1&refid=dcpagepl

Redaction, Publisher and Editorial Office

Instytut Kultury Fizycznej Uniwersytet Kazimierza Wielkiego w Bydgoszczy, Institute of Physical Education Kazimierz Wielki University in Bydgoszcz, Poland 85-091 Bydgoszcz ul. Sportowa 2  www.ukw.edu.pl Copyright by Instytut Kultury Fizycznej UKW w Bydgoszczy http://ojs.ukw.edu.pl/index.php/johs  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at https://dbh.nsd.uib.no/publiseringskanaler/erihplus/periodical/info?id=485984

SIC Science citation index (calculated on the basis of TCI and Page Rank) 0

Russian Impact factor 0.16

Indexed in Index Copernicus Journals Master List.

http://journals.indexcopernicus.com/Journal+of+Education+Health+and+Sport,p24782242,3.html

ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

The InfoBase Index IBI Factor for the year 2015 is 3.56 in InfoBase Index.com.

Website: www.infobaseindex.com

Universal Impact Factor 1.78 for year 2012. (http://www.uifactor.org/AppliedJournals.aspx)

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (https://pbn.nauka.gov.pl/journals/36616)

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ) http://elibrary.ru/contents.asp?titleid=37467

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski

(http://www1.bg.us.edu.pl/bazy/czasopisma/czasop_full.asp?id=3595)