Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zonisamide readily crosses the blood-brain barrier and is readily absorbed after oral administration with a Tmax of about 3 hr. The half-life of ZNA in epileptic patients is about 28 hr. Zonisamide has a broader therapeutic range than other antiepileptic drugs. Neurotoxic, hemapoietic, renal, and liver effects have been minimal in patients participating in controlled clinical studies. It is effective in several experimental models of epilepsy and in initial clinical trials has been shown to be effective in generalized tonic-clonic, simple, and complex partial seizures.
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PMID:Neuropharmacology of zonisamide, a new antiepileptic drug. 355 63

Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures), and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures (including those refractory to treatment with other antiepileptic drugs). Other generalised seizure types have also responded to therapy with zonisamide, although only small patient numbers were studied. Zonisamide has demonstrated efficacy equivalent to that of carbamazepine in patients with (mainly) partial seizures, and to that of valproic acid in a small study of children (n = 32) with generalised seizures. Animal studies suggest that zonisamide possesses a more favourable therapeutic index than most other antiepileptic drugs. However, clinical trials conducted to date, have not confirmed any overt tolerability advantage. Indeed, whereas the recommended therapeutic plasma zonisamide concentration is 20 mg/L, clinical investigations have associated adverse events with plasma zonisamide concentrations of > 30 mg/L, suggesting the usefulness of therapeutic drug monitoring. Moreover, although plasma concentrations of zonisamide are empirically regarded to be proportional to therapeutic doses in patients in Japan, nonlinear pharmacokinetics have been reported for this drug in patients in the US and may further complicate its use in this patient population. Additional pharmacokinetic studies will help to establish the change in pharmacokinetic profile that occurs with dosage titration in patients outside Japan. Among 700 patients treated with zonisamide in Europe/US, a high incidence of renal calculi (1.9%) has been noted, however, the causal relationship to zonisamide is disputed. Indeed, although urinary lithiasis has also been recorded for patients in Japan, the aetiology, incidence and spontaneous regression of this condition suggest that it is not a serious problem for this patient population. Until this difference is clarified, it is likely that zonisamide will find its greatest use in the treatment of patients in Japan. Like many other established antiepileptic drugs, available data suggest the propensity for zonisamide to alter the pharmacokinetic profile of other anticonvulsant agents, although severe interactions appear to be unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. 768 68

Zonisamide (ZNS)-induced behavior disorders are reported in a 1-year-old girl and a 3-year-old boy. Both patients, who had no previous developmental or mental problems, displayed secondarily generalized motor seizures. Serum concentrations of ZNS were not high, 8.8 and 12.3 micrograms/ml (effective range 10-30 micrograms/ml) respectively. Although many cases of ZNS-related psychotic reactions and/or behavior disorders have been reported, all affected patients had complex partial seizures (CPS) and had received combination therapy with phenytoin (PHT). Thus, whether the disorders were induced only by ZNS, by an interaction between ZNS and PHT, or by CPS could not be determined. In the children reported, however, ZNS clearly induced behavior disorders at plasma ZNS levels within or even below the therapeutic range.
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PMID:Zonisamide-induced behavior disorder in two children. 815 65

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.
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PMID:Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. 832 80

A brief review of epilepsy as a disease, anti-epileptic drugs and methods of evaluation of anti-epileptic drugs are presented as a background for assessment of zonisamide, which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. Chemically, zonisamide is classified as a sulphonamide and is unrelated to other anti-epileptic drugs. The mode of action of zonisamide remains unclear, but likely mechanisms are blockade of sodium and T-type calcium channels. It is also shown to have some neuroprotective effect against hypoxia and ischaemia. It has a liner pharmacokinetics with excellent oral bioavailability. Zonisamide has been approved for use in Japan for ten years prior to approval in USA and Europe. Clinical experience with zonisamide in Japan has documented its efficacy in the treatment of partial seizures (partial-onset generalised tonic-clonic, simple partial and/or complex partial seizures) and to a more variable extent, generalised tonic-clonic, generalised tonic (mainly seen in symptomatic generalised epilepsies including Lennox-Gastaut Syndrome) and compound/combination seizures. The efficacy and safety was confirmed in trials conducted in USA and Europe in adults as well as children. Zonisamide compares favourably with other newly introduced drugs and has the potential for development as a monotherapy for epilepsy.
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PMID:An assessment of zonisamide as an anti-epileptic drug. 1124 91

We report a case of adversive seizures featuring neck rotation and conjugate deviation induced by the hyperventilation maneuver. At the age of 6 years the patient suffered from conjugate deviation to the left. She herself felt no symptoms other than oculomotor symptoms. Hyperventilation induced an adversive seizure and ictal EEG showed sharp waves in the right frontal, central, and parietal areas. No brain image showed abnormal findings. Zonisamide completely attenuated her attacks. It is well known that hyperventilation induces absence seizures, and it has been reported that hyperventilation can induce complex partial seizures. However, no previous reports have described patients diagnosed as having adversive seizures with conjugate deviation induced by hyperventilation. We report the present case because, although its epileptogenesis is unknown, the patient is a rare case not only clinically but also electrophysiologically.
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PMID:A case of adversive seizures induced by hyperventilation. 1292 16

Zonisamide (Zonegran) has been used extensively worldwide (>2 million patient-years experience) for the effective treatment of a broad range of epilepsy indications. Four randomised, placebo-controlled trials (duration <or=6 months) in the United States and Europe (848 patients in total) have shown doses of zonisamide >or=300 mg/day to be efficacious in treating refractory partial seizures in adults. In a pivotal European study, zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency. Pooled data from all four placebo-controlled trials demonstrate an excellent tolerability and safety profile; adverse events are generally of mild-moderate severity with few leading to discontinuation, and incidence of serious adverse events is comparable to placebo. These data support the use of zonisamide in combination with commonly used antiepileptic drugs to provide efficacious and well-tolerated treatment for patients with refractory partial seizures.
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PMID:Zonisamide as adjunctive therapy for refractory partial seizures. 1631 44