142
Views
6
CrossRef citations to date
0
Altmetric
Drug Profile

Clinical pharmacology of levetiracetam for the treatment of epilepsy

, , &
Pages 339-350 | Published online: 10 Jan 2014

References

  • de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav.12(4), 540–546 (2008).
  • Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin. Emerg. Drugs12(3), 407–422 (2007).
  • Kwan P, Brodie MJ. Clinical trials of antiepileptic medications in newly diagnosed patients with epilepsy. Neurology60(11 Suppl. 4), S2–S12 (2003).
  • Perucca E, Meador KJ. Adverse effects of antiepileptic drugs. Acta Neurol. Scand. Suppl.181, 30–35 (2005).
  • Toledano R, Gil-Nagel A. Adverse effects of antiepileptic drugs. Semin. Neurol.28(3), 317–327 (2008).
  • Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol. Ther.85(2), 77–85 (2000).
  • Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin. Pharmacokinet.43(11), 707–724 (2004).
  • Patsalos PN, Berry DJ, Bourgeois BF et al. Antiepileptic drugs - best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia49(7), 1239–1276 (2008).
  • Klitgaard H, Verdru P. Levetiracetam: the first SV2A ligand for the treatment of epilepsy. Expert Opin. Drug Discov.2(11), 1537–1545 (2007).
  • Lynch BA, Lambeng N, Nocka K et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc. Natl Acad. Sci. USA101(26), 9861–9866 (2004).
  • Crowder KM, Gunther JM, Jones TA et al. Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proc. Natl Acad. Sci. USA96(26), 15268–15273 (1999).
  • Kaminski RM, Gillard M, Leclercq K et al. Proepileptic phenotype of SV2A-deficient mice is associated with reduced anticonvulsant efficacy of levetiracetam. Epilepsia DOI: 10.1111/j.1528-1167.2009.02089.x (2009) (Epub ahead of print).
  • Lynch JM, Tate SK, Kinirons P et al. No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy. Epilepsy Res.83(1), 44–51 (2009).
  • Kaminski RM, Matagne A, Leclercq K et al. SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy. Neuropharmacology54(4), 715–720 (2008).
  • Loscher W, Honack D, Rundfeldt C. Antiepileptogenic effects of the novel anticonvulsant levetiracetam (ucb L059) in the kindling model of temporal lobe epilepsy. J. Pharmacol. Exp. Ther.284(2), 474–479 (1998).
  • Margineanu DG, Matagne A, Kaminski RM, Klitgaard H. Effects of chronic treatment with levetiracetam on hippocampal field responses after pilocarpine-induced status epilepticus in rats. Brain Res. Bull.77, 282–285 (2008).
  • Yan HD, Ji-qun C, Ishihara K, Nagayama T, Serikawa T, Sasa M. Separation of antiepileptogenic and antiseizure effects of levetiracetam in the spontaneously epileptic rat (SER). Epilepsia46(8), 1170–1177 (2005).
  • Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia41(10), 1276–1283 (2000).
  • Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik IE. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology55(2), 236–242 (2000).
  • Shorvon SD, Lowenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia41(9), 1179–1186 (2000).
  • Glauser TA, Ayala R, Elterman RD et al. Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology66(11), 1654–1660 (2006).
  • Piña-Garza JE, Nordli D, Rating D et al. Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures. Epilepsia50(5), 1141–1149 (2009).
  • Tsai JJ, Yen DJ, Hsih MS et al. Efficacy and safety of levetiracetam (up to 2000 mg/day) in Taiwanese patients with refractory partial seizures: a multicenter, randomized, double-blind, placebo-controlled study. Epilepsia47(1), 72–81 (2006).
  • Heo K, Lee BI, Yi SD et al. Efficacy and safety of levetiracetam as adjunctive treatment of refractory partial seizures in a multicentre open-label single-arm trial in Korean patients. Seizure16(5), 402–409 (2007).
  • Wu XY, Hong Z, Wu X et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures. Epilepsia50(3), 398–405 (2009).
  • Murasaki M, Yagi K, Yamauchi T et al. Multicentre, double-blind, randomised, placebo-controlled, parallel-group study of add-on levetiracetam in Japanese patients with uncontrolled partial seizures. 6th Asian and Oceanian Epilepsy Congress. Kuala Lumpur, Malaysia, 16–19 November 2006, Abstract Book 62-63 (2006) (Abstract 256).
  • Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology68(6), 402–408 (2007).
  • Pohlmann-Eden B, van Paesschen W, Hallstrom Y et al. The KOMET study: an open-label, randomized, parallel-group trial comparing the efficacy and safety of levetiracetam with sodium valproate and carbamazepine as monotherapy in subjects with newly diagnosed epilepsy. Epilepsia49(Suppl. 7), 448–449 (2008).
  • Noachtar S, Andermann E, Meyvisch P et al. Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. Neurology70(8), 607–616 (2008).
  • Berkovic SF, Knowlton RC, Leroy RF, Schiemann J, Falter U. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy; Levetiracetam N01057 Study Group. Neurology69(18), 1751–1760 (2007).
  • French J, Edrich P, Cramer JA. A systematic review of the safety profile of levetiracetam: a new antiepileptic drug. Epilepsy Res.47(1-2), 77–90 (2001).
  • Hulhoven R, Rosillon D, Bridson WE, Meeus MA, Salas E, Stockis A. Effect of levetiracetam on cardiac repolarization in healthy subjects: a single-dose, randomized, placebo- and active-controlled, four-way crossover study. Clin. Ther.30(2), 260–270 (2008).
  • Levisohn PM, Mintz M, Hunter SJ, Yang H, Jones J; on behalf of the N01103 Levetiracetam Study Group. Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: a randomized, double-blind, placebocontrolled, non-inferiority trial. Epilepsia (2009) (In Press).
  • De La Loge C, Hunter S, Schiemann J, Yang H. Exploratory assessment of behavioral and emotional function in children and adolescents with partial-onset seizures treated with adjunctive levetiracetam in a randomized placebo-controlled trial. Neurology70(Suppl. 1), A74 (2008).
  • Strolin Benedetti M, Whomsley R, Nicolas JM, Young C, Baltes E. Pharmacokinetics and metabolism of 14C-levetiracetam, a new antiepileptic agent, in healthy volunteers. Eur. J. Clin. Pharmacol.59(8–9), 621–630 (2003).
  • Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin. Pharmacokinet.45(4), 351–363 (2006).
  • Coupez R, Straetemans R, Sehgal G, Stockis A, Lu ZS. Levetiracetam: relative bioavailability and bioequivalence of a 10% oral solution (750 mg) and 750-mg tablets. J. Clin. Pharmacol.43(12), 1370–1376 (2003).
  • Hirsch LJ, Arif H, Buchsbaum R et al. Effect of age and comedication on levetiracetam pharmacokinetics and tolerability. Epilepsia48(7), 1351–1359 (2007).
  • Radtke RA. Pharmacokinetics of levetiracetam. Epilepsia42(Suppl. 4), 24–27 (2001).
  • Nicolas JM, Collart P, Gerin B et al.In vitro evaluation of potential drug interactions with levetiracetam, a new antiepileptic agent. Drug Metab. Dispos.27(2), 250–254 (1999).
  • Otoul C, De Smedt H, Stockis A. No evidence for pharmacokinetic interaction of levetiracetam with other antiepileptic drugs in Japanese and Western adults with epilepsy. Epilepsia47(Suppl. 3), 47 (2006).
  • Otoul C, De Smedt H, Stockis A. Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy. Epilepsia48(11), 2111–2115 (2007).
  • Levy RH, Ragueneau-Majlessi I, Baltes E. Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Epilepsy Res.46(2), 93–99 (2001).
  • Ragueneau-Majlessi I, Levy RH, Meyerhoff C. Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res.47(1–2), 55–63 (2001).
  • Ragueneau-Majlessi I, Levy RH, Janik F. Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia43(7), 697–702 (2002).
  • Betts T, Waegemans T, Crawford P. A multicentre, double-blind, randomized, parallel group study to evaluate the tolerability and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy. Seizure9(2), 80–87 (2000).
  • Gidal BE, Baltès E, Otoul C, Perucca E. Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. Epilepsy Res.64(1–2), 1–11 (2005).
  • Pigeolet E, Jacqmin P, Sargentini-Maier ML, Stockis A. Population pharmacokinetics of levetiracetam in Japanese and Western adults. Clin. Pharmacokinet.46(6), 503–512 (2007).
  • Toublanc N, Sargentini-Maier M-L, Lacroix B, Jacqmin P, Stockis A. Retrospective population pharmacokinetic analysis of levetiracetam in children and adolescents with epilepsy: dosing recommendations. Clin. Pharmacokinet.47(5), 333–341 (2008).
  • Fountain NB, Conry JA, Rodríguez-Leyva I et al. Prospective assessment of levetiracetam pharmacokinetics during dose escalation in 4- to 12-year-old children with partial-onset seizures on concomitant carbamazepine or valproate. Epilepsy Res.74(1), 60–69 (2007).
  • French J. Use of levetiracetam in special populations. Epilepsia42(Suppl. 4), 40–43 (2001).
  • Brockmoller J, Thomsen T, Wittstock M, Coupez R, Lochs H, Roots I. Pharmacokinetics of levetiracetam in patients with moderate to severe liver cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver function tests. Clin. Pharmacol. Ther.77(6), 529–541 (2005).
  • Zhao Q, Jiang J, Li X, Lu ZS, Hu P. Single-dose pharmacokinetics of levetiracetam in healthy Chinese male subjects. Br. J. Clin. Pharmacol.63(5), 614–617 (2007).
  • Glauser TA, Mitchell WG, Weinstock A et al. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia48(6), 1117–1122 (2007).
  • Pellock JM, Glauser TA, Bebin EM et al. Pharmacokinetic study of levetiracetam in children. Epilepsia42(12), 1574–1579 (2001).
  • Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu. Rev. Pharmacol. Toxicol.48, 303–332 (2008).
  • Toublanc N, Lovern M, Sargentini-Maier M-L, Stockis A. Population pharmacokinetic analysis of levetiracetam in pediatric patients with epilepsy aged 1 month to 16 years. Epilepsia50(Suppl. 4), 131 (2009).
  • Adab N. Therapeutic monitoring of antiepileptic drugs during pregnancy and in the postpartum period: is it useful? CNS Drugs20(10), 791–800 (2006).
  • Brodtkorb E, Reimers A. Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy. Seizure17(2), 160–165 (2008).
  • Westin AA, Reimers A, Helde G, Nakken KO, Brodtkorb E. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure17(2), 192–198 (2008).
  • Pennell PB, Koganti A, Helmers SL et al. The impact of pregnancy and childbirth on the elimination of levetiracetam. Epilepsia46(Suppl. 8), 89 (2005).
  • Tomson T, Palm R, Kallen K et al. Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia48(6), 1111–1116 (2007).
  • Johannessen SI, Helde G, Brodtkorb E. Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia46(5), 775–777 (2005).
  • Allegaert K, Lewi L, Naulaers G, Lagae L. Levetiracetam pharmacokinetics in neonates at birth. Epilepsia47(6), 1068–1069 (2006).
  • Rhodin MM, Anderson BJ, Peters AM et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr. Nephrol.24(1), 67–76 (2009).
  • Guo T, Oswald LM, Mendu DR, Soldin SJ. Determination of levetiracetam in human plasma/serum/saliva by liquid chromatography-electrospray tandem mass spectrometry. Clin. Chim. Acta375(1–2), 115–118 (2007).
  • Jain DS, Subbaiah G, Sanyal M, Pal U, Shrivastav PS. Determination of levetiracetam in human plasma by liquid chromatography/electrospray tandem mass spectrometry and its application to bioequivalence studies. Rapid Commun. Mass Spectrom.20(17), 2539–2547 (2006).
  • Lancelin F, Franchon E, Kraoul L et al. Therapeutic drug monitoring of levetiracetam by high-performance liquid chromatography with photodiode array ultraviolet detection: preliminary observations on correlation between plasma concentration and clinical response in patients with refractory epilepsy. Ther. Drug. Monit.29(5), 576–583 (2007).
  • Martens-Lobenhoffer J, Bode-Boger SM. Determination of levetiracetam in human plasma with minimal sample pretreatment. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.819(1), 197–200 (2005).
  • Pucci V, Bugamelli F, Mandrioli R, Ferranti A, Kenndler E, Raggi MA. High-performance liquid chromatographic determination of levetiracetam in human plasma: comparison of different sample clean-up procedures. Biomed. Chromatogr.18(1), 37–44 (2004).
  • Rouits E, Burton I, Guenole E, Troenaru M, Stockis A, Sargentini-Maier M-L. Pharmacokinetics of levetiracetam XR 500 mg tablets. Epilepsy Res.84(2–3), 224–231 (2009).
  • Snoeck E, Stockis A. Dose–response population analysis of levetiracetam add-on treatment in refractory epileptic patients with partial onset seizures. Epilepsy Res.73(3), 284–291 (2007).
  • Johannessen SI, Battino D, Berry DJ et al. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther. Drug Monit.25(3), 347–363 (2003).
  • Johannessen SI, Tomson T. Pharmacokinetic variability of newer antiepileptic drugs: when is monitoring needed? Clin. Pharmacokinet.45(11), 1061–1075 (2006).
  • Lins RL, Otoul C, de Smedt F, Coupez R, Stockis A. Comparison of plasma and saliva concentrations of levetiracetam following administration orally as a tablet and as a solution in healthy adult volunteers. Int. J. Clin. Pharmacol. Ther.45(1), 47–54 (2007).
  • Matías-Guiú J, Molins A, Mauri JA, Villar E. Acceptability and tolerability of levetiracetam as oral solution (the ‘Solucion’ study). Epilepsia48(Suppl. 6), 341 (2007).
  • Ramael S, de Smedt F, Toublanc N et al. Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects. Clin. Ther.28(5), 734–744 (2006).
  • Ramael S, Daoust A, Otoul C et al. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia47(7), 1128–1135 (2006).
  • Snoeck E, Jacqmin P, Sargentini-Maier ML, Stockis A. Modeling and simulation of intravenous levetiracetam pharmacokinetic profiles in children to evaluate dose adaptation rules. Epilepsy Res.76(2–3), 140–147 (2007).
  • Baulac M, Brodie MJ, Elger CE et al. Levetiracetam intravenous infusion as an alternative to oral dosing in patients with partial-onset seizures. Epilepsia48, 589–592 (2007).
  • Otoul C, Rouits E, Burton I et al. Single dose bioequivalence between levetiracetam 2 × 750 mg XR tablets and 3 × 500 mg XR tablets and food effect on 2 × 750 mg XR tablets in healthy subjects. Epilepsia49(Suppl. 7), 446 (2008).
  • Rouits E, Lovern M, Sargentini-Maier M-L, Stockis A. Population pharmacokinetics of levetiracetam extended-release 500 mg tablets. Epilepsia49(Suppl. 7), 451–452 (2008).
  • Peltola J, Coetzee C, Jimenez F et al. Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: a double-blind, randomized, placebo-controlled trial. Epilepsia50(3), 406–414 (2009).
  • Schoemaker R, Snoeck E, Stockis A, Otoul C, Sargentini-Maier M-L. Dose–response analysis of levetiracetam extended- and immediate-release formulations in adults with partial onset seizures. Epilepsia49(Suppl. 7), 452–453 (2008).
  • Richy FF, Banerjee S, Gervasoni C, Grossman P, Helmers S. Safety profile of levetiracetam extended release as compared to immediate release: an indirect comparison using a meta-analytic approach. Epilepsia49(Suppl. 7), 449–450 (2008).
  • Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res.83(1), 1–43 (2009).
  • Meador KJ, Pennell PB, Harden CL et al; The HOPE workgroup. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology71(14), 1109–1117 (2008).

Websites

  • WHO collaborating centre for drug statistics methodology: defined daily doses (DDD) www.whocc.no/atcddd
  • Snoeck E, Schoemaker R, Stockis A, Otoul C, Sargentini-Maier M-L. Levetiracetam exposure-response analysis in children with partial-onset seizures. Abstracts of the Annual Meeting of the Population Approach Group in Europe, 17 (2008) (Abstract 1403) (ISSN 1871-6032). www.page-meeting.org/?abstract=1403

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.