Levetiracetam in the treatment of epilepsy

Abstract

Epilepsy is a common chronic disorder that requires long-term antiepileptic drug therapy. Approximately one half of patients fail the initial antiepileptic drug and about 35% are refractory to medical therapy, highlighting the continued need for more effective and better tolerated drugs. Levetiracetam is an antiepileptic drug marketed since 2000. Its novel mechanism of action is modulation of synaptic neurotransmitter release through binding to the synaptic vesicle protein SV2A in the brain. Its pharmacokinetic advantages include rapid and almost complete absorption, minimal insignifi cant binding to plasma protein, absence of enzyme induction, absence of interactions with other drugs, and partial metabolism outside the liver. The availability of an intravenous preparation is yet another advantage. It has been demonstrated effective as adjunctive therapy for refractory partial-onset seizures, primary generalized tonic-clonic seizures, and myoclonic seizures of juvenile myoclonic epilepsy. In addition, it was found equivalent to controlled release carbamazepine as fi rst-line therapy for partial-onset seizures, both in effi cacy and tolerability. Its main adverse effects in randomized adjunctive trials in adults have been somnolence, asthenia, infection, and dizziness. In children, the behavioral adverse effects of hostility and nervousness were also noted. Levetiracetam is an important addition to the treatment of epilepsy.

Levetiracetam Rectal Administration in Healthy Dogs

“…Although 5–40 μg/mL is the typically reported therapeutic range, these values are extrapolated from human values and the true therapeutic range in both humans and dogs is not well established. There is moderate variability in serum concentrations between individuals with good and poor seizure control and in those with and without evidence of adverse effects 33. We have therefore used the term “target range” to describe the range currently used as a goal for seizure control with minimal adverse effects in dogs.…”

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“…LEV de metabolize edilmeden büyük oranda böbreklerden atılmaktadır. [23,24] Sitokrom p450 enzim sistemi ile ilişkisi olmayan bu ilaçların lipid metabolizması üzerine olan etkilerini araştıran az sayıda çalışma yapılmıştır. [4,7] Literatürde LEV, LTG ve KBZ tedavilerinin kardiyovaskü-ler risk faktörlerine etkisini araştıran bir çalışmada, LEV ve LTG'nin lipid profili üzerine bir etkisi olmadığı ancak KBZ kullanan grubun daha yüksek kolesterol ve LDL değerle-rine sahip olduğu bildirilmiştir.…”

Can the Pharmaceutical Drug Keppra (Levetiracetam) Be Used as a Therapeutic Agent for Patients with Butterfly Glioblastoma?

“…8,9 Despite the behaviors of multiple antiepileptic drugs (AEDs), LEV inhibits calcium release by binding to a synaptic vesicle protein and modulates seizure-activity with individuals diagnosed with chronic epilepsy. 10 Lacking anticonvulsant activity in classic acute seizure models used for AED screening, LEV is unable to promote a fully elucidated mechanism of action for the seizure prevention, but it up regulates glutamate transporters, resulting in the possibility of increased neuroprotection.…”

“…However, the evidence of adjunctive efficacy in juvenile myoclonic epilepsy has prompted use as initial monotherapy in juvenile myoclonic epilepsy. 10 Thus, without comparing it to other AEDs, the use of LEV as an initial monotherapy cannot be strongly supported. Overall, LEV stands as a well-tolerated AED in the realm of therapeutic agency due to the fact that it has a straightforward pharmacokinetic profile in which, it is almost completely eliminated by renal excretion, has a minimal protein binding and consequently has no interaction with other drugs.…”