Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seizure frequency (number/week). Tolerability was assessed by adverse events, laboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lower median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizures per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment with levetiracetam compared with only 14% with placebo. Levetiracetam was well tolerated. The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.
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PMID:Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy. 1107 81

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of levetiracetam are reviewed. Levetiracetam is an adjunctive treatment for partial-onset epileptic seizures. This drug inhibits seizure activity via a mechanism that does not involve excitatory or inhibitory neuronal pathways. Oral bioavailability is about 100%, and food does not alter absorption. Levetiracetam is minimally plasma protein bound (10%). Peak time to absorption after oral administration is one hour, and steady state is achieved in two days with twice-daily administration. Three clinical studies have demonstrated levetiracetam's ability to reduce seizure frequency in patients with partial-onset epilepsy. The most commonly reported adverse effects in clinical trials were somnolence, dizziness, infection, and asthenia. The potential for interactions with medications that are hepatically metabolized is minimal. The starting dosage is 500 mg twice a day; the maximum dosage is 3000 mg/day within four weeks. Levetiracetam is effective as an adjunctive treatment of partial-onset epilepsy with or without secondary generalization.
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PMID:Levetiracetam. 1144 76

Levetiracetam (LEV) is a new antiepileptic drug with a promising preclinical profile involving both anticonvulsant and antiepileptogenic effects in kindling models. The latter stimulated the present study to compare its neuroprotective properties with the potent and selective, non-competitive NMDA antagonist, MK-801, in the rat middle cerebral artery occlusion model. Twenty-four hours after a transient occlusion of 90 minutes the animals were sacrificed and infarct volume and lesion distribution were determined from stained coronal sections. LEV was administered by intraperitoneal (i.p.) bolus injections of 5.5, 11, 22 and 44 mg x kg(-1), 30 minutes before occlusion followed by a continuous 24 hour i.p. infusion of 1.25, 2.6, 5.1 and 10.2 mg x kg(-1) per hour, respectively. LEV administration did not alter body temperature but reduced the infarct volume by 33% (P< 0.05) at the highest dose tested. An i.p. bolus injection of 0.04, 0.12 and 0.4 mg x kg(-1) of MK-801 followed by continuous i.p. infusion of 0.036, 0.108 and 0.36 mg x kg(-1) per hour, reduced the infarct volume by 49, 51 and 74% (P< 0.05), respectively. However, only the highest dose of MK-801 induced a significant reduction in the infarct volume (P< 0.05) and this was associated with hypothermia. These results suggest that LEV possesses neuroprotective properties which may be relevant for its antiepileptogenic action.
Seizure 2001 Jun
PMID:Neuroprotective properties of the novel antiepileptic drug levetiracetam in the rat middle cerebral artery occlusion model of focal cerebral ischemia. 1146 25

The choice of an antiepileptic drug depends firstly on its efficacy in specific seizure types and epilepsies. However, it is imperative to consider whether possible adverse events will outweigh any benefits. The advantages and disadvantages of vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine and felbamate are considered in some detail, and oxcarbazepine, stiripentol, remacemide, zonisamide and levetiracetam more briefly. Vigabatrin is effective for partial seizures and infantile spasms, but visual field defects are limiting its use. Lamotrigine has a wide spectrum, needs to be prescribed with care. Gabapentin is unlikely to cause adverse effects, but has relatively poor efficacy. Topiramate is widely effective, but can be poorly tolerated. Tiagabine is relatively untried in childhood epilepsies. The use of felbamate is restricted to severe refractory epilepsies. Stiripentol can be effective in severe myoclonic epilepsy in infancy. Zonisamide has a special place in the progressive myoclonus epilepsies. Levetiracetam, remacemide and oxcarbazepine have been used mainly for partial seizures: further studies of their roles in other circumstances are required.
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PMID:Newer antiepileptic drugs: advantages and disadvantages. 1150 96

Levetiracetam is a new antiepileptic drug (AED) devoid of anticonvulsant activity in the two classic screening models for AEDs, the maximal electroshock and pentylenetetrazol seizure tests in both mice and rats. This contrasts a potent seizure suppression in genetic and kindled mice and rats and against chemoconvulsants inducing partial seizures in rats. The highly selective action in "epileptic" animals distinguishes levetiracetam from classic and other new AEDs that have nearly equipotent effects in normal and "epileptic" animals. Levetiracetam induces minor behavioral alterations in normal and in kindled mice and rats. This results in an unusually high safety margin in animal models reflecting both partial and primary generalized epilepsy. Furthermore, experiments in the kindling model suggest that levetiracetam may possess antiepileptogenic properties due to a potent ability to prevent the development of kindling in mice and rats at doses devoid of adverse effects. Electrophysiologic recordings from different experimental models suggest that levetiracetam exerts a selective action against abnormal patterns of neuronal activity, which probably explains its selective protection in epileptic animals and its unique tolerability. This effect appears to derive from one or more novel mechanisms of action that do not involve a conventional interaction with traditional drug targets implicated in the modulation of inhibitory and excitatory neurotransmission. Instead, ligand-binding assays have disclosed a brain-specific binding site for levetiracetam. These studies reveal a unique preclinical profile of levetiracetam, distinct from that of all known AEDs, suggesting that levetiracetam could represent the first agent in a new class of AEDs.
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PMID:Levetiracetam: the preclinical profile of a new class of antiepileptic drugs? 1156 19

Levetiracetam is a novel antiepileptic drug (AED) with favorable pharmacologic characteristics and demonstrated activity in improving seizure control. Three multicenter double-blind, placebo-controlled studies were conducted in 904 patients with refractory partial-onset seizures. Patients were required to have a minimum of two or four seizures per week (depending on the study) and were maintained on a stable regimen of one or two AEDs at baseline that was continued during the study period. Patients ranged in age from 14 to 70 years, with a mean age of approximately 37 years. After an 8- to 12-week baseline period, patients were randomized and had doses titrated upward every 2 weeks over a period of 4 weeks to a target dose of 1,000, 2,000, or 3,000 mg/day of levetiracetam or placebo. Treatment was continued for a 12- to 14-week evaluation phase followed by an optional open-label treatment phase. The treatment period consisted of the dose titration period combined with the evaluation period. The median percentage reduction in seizure frequency (over placebo) was calculated for each of the levetiracetam treatment groups over the entire treatment period. For all levetiracetam dose groups, in all studies, reduction in seizure frequency over placebo was statistically significant (p < or = 0.001). Median percentage reductions were 26.1% and 17.1% in the 1,000-mg/day groups (study 1 and study 2, respectively), 21.4% in the 2,000-mg/day group (study 2), and 30.1% and 23.0% in the 3,000-mg/day groups (study 1 and study 3, respectively). The percentage of patients achieving a > or = 50% reduction from baseline in seizure frequency compared with the treatment period was 37.1% and 20.8% in the 1,000-mg/day groups (study 1 and study 2, respectively), 35.2% in the 2,000-mg/day group (study 2), and 39.6% and 39.4% in the 3,000-mg/day groups (study 1 and study 3, respectively). These responder rates were significantly higher than those for placebo (p < 0.001 for all comparisons). Levetiracetam was generally well tolerated in all studies. Results from these three pivotal studies demonstrate that levetiracetam, as adjunctive therapy, is a safe and effective treatment for refractory partial-onset seizures in adults.
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PMID:Efficacy of levetiracetam: a review of three pivotal clinical trials. 1156 23

Levetiracetam was approved in November 1999 as add-on therapy for the treatment of partial-onset seizures in adults (age 16 years and older). This review focuses on recently published data from four well-controlled studies in patients with partial-onset seizures with or without secondary generalization. When levetiracetam was given along with other antiepileptic drugs (AEDs), the most frequently reported adverse events were central nervous system related. Adverse events were usually mild to moderate in intensity, with the most frequently reported events occurring predominantly during the first 4 weeks of treatment. No relationship was apparent between the dose of levetiracetam and the most commonly reported adverse events in well-controlled clinical trials within the recommended dose range of 1,000-3,000 mg/day. Levetiracetam is a Pregnancy Category C drug. Overall, when used in combination with other AEDs, levetiracetam was generally well tolerated as add-on treatment for partial-onset seizures.
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PMID:Safety profile of levetiracetam. 1156 24

Levetiracetam was recently approved as adjunctive therapy for partial onset seizures. The authors conducted an open-label trial of levetiracetam in eight patients with chronic myoclonus. Patients were assessed by using the Unified Myoclonus Rating Scale. Levetiracetam was well tolerated. Three of five patients with cortical myoclonus experienced reductions in their myoclonus scores, providing support for a larger, placebo-controlled trial in cortical myoclonus.
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PMID:A pilot tolerability and efficacy study of levetiracetam in patients with chronic myoclonus. 1157 47

Levetiracetam is a new antiepileptic drug, structurally and mechanistically dissimilar to other marketed antiepileptic drugs. It is effective in reducing partial seizures in patients with epilepsy, both as adjunctive treatment and as monotherapy. Levetiracetam has many therapeutic advantages for patients with epilepsy. It has favorable pharmacokinetic characteristics (good bioavailability, linear pharmacokinetics, insignificant protein binding, lack of hepatic metabolism, and rapid achievement of steady-state concentrations) and a low potential for drug interactions. Recommended starting dosages are considered to be clinically effective; therefore, patients can have some protection from seizures soon after they begin levetiracetam. The most common adverse effects observed with levetiracetam are mild and include somnolence, asthenia, and dizziness. Clinical experience and data from meta-analyses indicate that levetiracetam is well tolerated, with efficacy comparable or slightly better than that observed with other new antiepileptic drugs. Levetiracetam may be particularly useful in patients who are unresponsive to other antiepileptic drugs, patients receiving drugs with increased potential for drug interactions, or those with hepatic impairment.
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PMID:Levetiracetam: a novel antiepileptic drug. 1171 11

Levetiracetam is a new antiepileptic drug with a chemical structure similar to piracetam, but different pharmacological properties. The pharmacokinetic profile of levetiracetam closely approximates the ideal characteristics expected of an antiepileptic drug: good bioavailability, linear kinetics, rapid achievement of steady-state concentrations, minimal protein binding and minimal metabolism. It has been approved as add-on therapy for the treatment of partial-onset seizures in adults. Its efficacy has been proved through four pivotal double-blind, aleatorized, placebo-controlled trials. Levetiracetam is well-tolerated and the incidence of adverse events is similar to placebo. There is no evidence of any specific interactions between levetiracetam and digoxin, warfarin, probenecid or other antiepileptic drugs. Preclinical studies have shown potential efficacy against generalized seizures. Antidystonic and antimyoclonic effects have been also suggested. There are few data of its efficacy on monotherapy and pediatric population.
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PMID:[Levetiracetam]. 1174 23


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