Antiepileptic drugs levetiracetam

Lynch BA et al The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A 2004 101 9861. [PMID 15210974]... 

Antiepileptic drugs Levetiracetam Topiramate Valproic acid... 

Noyer M, Gillard M, Matagne A, et al. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur J Pharmacol 1995 286 137-146. 

Giuliano Hiersemenzel R, Baltes E, Johnscher G, Janik F, Weber W. Influence of a new antiepileptic drug (Levetiracetam, ucb L059) on the pharmacokinetics and plarmacodynamics of oral contraceptives. Epilepsia (1996) 37,90. 

Ratnaraj, N. Doheny, H.C. Patsalos, P.N. A micromethod for the determination of the new antiepileptic drug levetiracetam (ucb L059) in serum or plasma by high performance liquid chromatography, Ther.Drug Monit., 1996,18, 154-157. [LOQ 5 p,M]... 

Pharmacology Levetiracetam is chemically unrelated to other antiepileptic drugs. The precise mechanism by which levetiracetam exerts its antiepileptic effect is unknown. 

Side effects. Detailed safety studies show that levetiracetam is well tolerated, the most frequent side effects reported being somnolence, asthenia and dizziness. To date, levetiracetam would appear to be a highly effective new antiepileptic drug with an excellent safety and tolerability profile. Few drug interactions have been reported so far. The efficacy and safety of the drug have been established as add-on therapy for refractory partial onset seizures with or without secondary generalization and there is now evidence of its efficacy in monotherapy. 

The clinical pharmacology and adverse effects of some new antiepileptic drugs (ganaxolone, levetiracetam, losi-gamone, pregabalin, remacemide, rufinamide, stiripentol, and zonisamide) have been reviewed (1). 

The efficacy and tolerability of levetiracetam 1-2 g/day as add-on therapy have been studied in 324 patients with refractory partial seizures (9). Levetiracetam did not affect the plasma concentrations of other antiepileptic drugs or alter vital signs or laboratory measurements. The most commonly reported adverse effects in patients taking levetiracetam were weakness, headache, and somnolence. 

French J, Edrich P, Cramer JA. A systematic review of the safety profile of levetiracetam a new antiepileptic drug. Epilepsy Res 2001 47(l-2) 77-90. 

Bakes, S. et al. (2007) Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse... 

Antiepileptic drugs in Phase III clinical trials are shown in Figure 20.12. Talampanel is a 2,4-benzodiazepine that is a AMPA/KA receptor antagonist. RWJ-333369 is a monocarbamate antagonist at KA receptors. Rufinamide is a 1,2,3-triazole carboxamide that blocks sodium channels. Soretilide has a mechanism of action similar to that of CBZ, and brivaracetam and seletracetam are derivatives of S-(-)-levetiracetam for treatment of myoclonic seizures. 

Margineanu GD. Inhibition of neuronal hypersynchrony in vitro differentiates levetiracetam from classical antiepileptic drugs. Pharmacol Res 2000 42 281-285. 

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

Up to a few years ago, the association between the risk of suicidal ideation and behavior and the use of antiepileptic drugs had been explored in very few studies. In an observational study of 517 consecutive patients taking levetiracetam, four (0.7%) reported suicidal ideation [Id ]. The incidence of suicidal ideation and behavior resulting from antiepileptic drug exposure in clinical trials is unknown, because most published data group all psychiatric adverse events together rather than reporting suicidality by itself [15, 16, 17 ]. 

Drug overdose Of 16 796 toxic exposures to antiepileptic drugs (phenytoin, valproic acid, and carbamazepine) in the USA in 2006, 12 resulted in death, as reported by the US Toxic Surveillance System [67 ]. Some specific problems determined by overdose of some old and new antiepileptic drugs have been briefly reviewed. For example, topiramate can cause a significant metabolic acidosis, lamotrigine Stevens-Johnson syndrome, oxcarbazepine hyponatremia, and levetiracetam psychosis. Possible adoption of guidelines for critical care management of overdose are discussed. 

Levetiracetam and phenytoin have been retrospectively compared in the prophylaxis of early and late postoperative seizures in 315 patients [182 ]. Levetiracetam (n = 105) was at least as effective as phenytoin ( = 210) and significantly better tolerated. Adverse effects that prompted a change in antiepileptic drug therapy occurred in one patient taking levetiracetam, who had visual hallucinations, compared with 38 patients taking phenytoin (18%). In patients who were followed for at least 1 year and developed epilepsy, levetiracetam also had a higher retention rate. 

Teratogenicity Of 147 patients 2% had chUdren with a major congenital malformation and 4.8% had a minor anomaly in all these patients, levetiracetam was associated with the use of other antiepileptic drugs [203 ]. 

Ivanova, M., Piunti, A., Marziali, E., Komarova, N., Raggi, M., Kenndler, E. 2003, Microemulsion electrokinetic chromatography applied for separation of levetiracetam from other antiepileptic drugs in polypharmacy. Electrophoresis 24, 992. 

Other therapeutic drug classes currently quantified by LC—MS in clinical laboratories include antiepileptic medications (levetiracetam [23]), immunosuppressive/antivirals (leflunomide [24]), and synthetic steroids (prednisolone, methylprednisolone, dexamethasone, and others [25]). 

Phabphal K, Geater A, limapichat K, Sathirapanya P, Setthawatcharawanich S, Leelawattana R. Effect of switching hepatic enzyme-inducer antiepileptic drug to levetiracetam on bone mineral density, 25 hydrox)rvitamin D, and parath)froid hormone in young adult patients with epilepsy. Epilepsia June 2013 54(6) e94-8. 

Some nonproteinogenic amino acids, produced enzymatically, are shown in Table 29.4 for example, L-homophenylalanine, a key intermediate of levetiracetam and brivaracetam applicable as antiepileptic drugs, or D-fluoroalanine, a key intermediate of antibiotics inactivating the bacterial D-alanine transaminase. In Table 29.4 a selection of proteinogenic and nonproteinogenic amino acids, the used biocatalysts, synthesis strategies, and the substrates used are listed. 

Nicolas, J.-M. et al.. In vitro evaluation of potential drug interactions with levetiracetam, a new antiepileptic agent, Drug Metab. Dispos., 27 250-254, 1999. 

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