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PubMed1994

[Zonisamide monotherapy against absence attacks: report of two cases].

We report two cases of absence seizures, in which zonisamide monotherapy was effective. In one case the attacks recurred 6 months after the beginning of zonisamide therapy but ceased again with an increase of the dosage. The EEG prior to treatment showed 3 Hz generalized spike-wave patterns and 3 Hz high voltage slow wave burst in the right occipital area in one case, and 3.5-4 Hz generalized spike-wave patterns and focal spike-wave complexes in the left frontal to central areas in the other. One of the generalized spike-wave patterns were preceded by right occipital delta wave burst in one case, and bilateral occipital sharp-wave complex in the other. It is suggested that zonisamide monotherapy may be effective against absence seizures with focal paroxysmal discharges.

Child↗
PubMed1993

Inhibitory effect of zonisamide on human carbonic anhydrase in vitro.

We examined the relative potencies of zonisamide (CAS 68291-97-4) to acetazolamide in inhibiting carbonic anhydrases in human erythrocytes and purified human carbonic anhydrase I and II in vitro and found them to be about 1/150, 1/8 and 1/188, respectively. The IC50 values of zonisamide and acetazolamide for the inhibition of erythrocyte enzymes were close to those of purified carbonic anhydrase II. This result indicates that zonisamide actually differs from acetazolamide in their actions on the physiological events which are coupled with CO2 hydration in vivo.

Acetazolamide↗
PubMed2002

A possible role for zonisamide in treating neuropathic pain: a case of idiopathic polyneuropathy.

Anti-epilepsy medications have frequently been used in the treatment of neuropathic pain to reduce the transmission of nociceptive signals.(1,2) Zonisamide is a sulfonamide drug that was approved in 2000 for the adjunctive treatment of partial seizures in adults. Because of the unique combination of mechanisms through which zonisamide functions, it has potential to be a useful option in the treatment of refractory neuropathic pain. We present the case of a patient with refractory neuropathic pain related to idiopathic polyneuropathy, who responded to adjunctive treatment with zonisamide.

Journal Article↗
PubMed2007

Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of daily doses of 25, 50, and 100 mg of zonisamide (ZNS) administered as adjunctive treatment in patients with Parkinson disease (PD). METHODS: We conducted a multicenter, randomized, double-blind, parallel-treatment, placebo-controlled study in Japan. Patients with PD who showed insufficient response to levodopa treatment were given placebo for 2 weeks and then treated for 12 weeks with 25, 50, or 100 mg/day of ZNS or placebo, in addition to levodopa, followed by a 2-week dose-reduction period. The primary endpoint was change from baseline in the total score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III at the final assessment point. Secondary endpoints included changes from baseline in total daily "off" time; total scores of UPDRS Parts I, II, and IV; and Modified Hoehn and Yahr Scale score. Safety analysis was based on the incidence of adverse events. RESULTS: There was significant improvement in the primary endpoint in the 25-mg and 50-mg groups vs placebo. The duration of "off" time was significantly reduced in the 50-mg and 100-mg groups vs placebo. Dyskinesia was not increased in ZNS groups. The incidence of adverse effects was similar between the 25-mg, 50-mg, and placebo groups but higher in the 100-mg group. CONCLUSIONS: Zonisamide is safe, effective and well tolerated at 25 to 100 mg/day as an adjunctive treatment in patients with Parkinson disease.

Adult↗
PubMed1998

Steady-state pharmacokinetics of zonisamide, an antiepileptic agent for treatment of refractory complex partial seizures.

A 56-day pharmacokinetic study of zonisamide was conducted in 24 healthy volunteers. Steady state was achieved in 29 days including two dose escalations, and in an average of 15 days from the last dose adjustment. Twice-daily administration of 200 mg every 12 hours produced a 14% serum level fluctuation at steady state. After once-daily administration of 400 mg, a 27% serum level fluctuation was observed. The terminal-phase half-life after the last dose was 63 to 69 hours, which is consistent with the half-life of 52 to 60 hours found in single-dose studies. This result demonstrates that zonisamide is not an autoinducer. Serum oral clearance of 0.60 to 0.71 L/hr (0.121-0.132 mL/min/kg) was similar to that observed in other multiple-dose studies.

Anticonvulsants↗
PubMed1987

Neuropharmacology of zonisamide, a new antiepileptic drug.

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.

Animals↗
PubMed1994

Simple and sensitive assay of zonisamide in human serum by high-performance liquid chromatography using a solid-phase extraction technique.

A rapid and sensitive method for the assay of zonisamide in serum was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. A 20-microliter volume of human serum was first purified with a Bond-Elut cartridge column. Then, the methanol eluate was injected onto a reversed-phase HPLC column with a UV detector. The mobile phase was acetonitrile-methanol-distilled water (17:20:63, v/v) and the detection wavelength was 246 nm. The detection limit was 0.1 micrograms/ml in serum. The coefficients of variation were 4.2-5.6% and 5.1-9.1% for the within-day and between-day assays, respectively. This method can be used for clinical pharmacokinetic studies of zonisamide in serum even in infant patients with epilepsy.

Anticonvulsants↗
PubMed2006

Zonisamide eradicated paroxysmal headache with EEG abnormalities triggered by hypertensive encephalopathy due to purpura nephritic syndrome.

Generally, prognosis of hypertensive encephalopathy in childhood is favorable. We reported a 5-year-old girl who presented with a headache attack and EEG abnormalities after hypertensive encephalopathy due to purpura nephritis. The patient had suffered from hypertensive encephalopathy due to purpura nephritis, which soon ameliorated. Five months later, she developed attacks of headache, vomiting and disturbed consciousness with left side-predominant EEG abnormalities. Although carbamazepine and sodium valproate failed to improve her condition, zonisamide eradicated both the symptoms and EEG abnormalities, and an attack has not reoccurred for 5 years since completion of her treatment. It is noteworthy that delayed-onset complications can occur in child hypertensive encephalopathy, cases of which should be followed up prudently. Zonisamide should be considered for treatment of attacks of headaches with an epileptic character.

Anticonvulsants↗
PubMed2006

Zonisamide or levetiracetam for adults with cyclic vomiting syndrome: a case series.

BACKGROUND & AIMS: Management of cyclic vomiting syndrome in adults is limited by the small number of effective medications for maintenance therapy. The clinical response to treatment with 2 newer antiepileptic drugs was evaluated retrospectively to see whether they might have a prophylactic role in this syndrome. METHODS: Outpatient records from 20 adult patients with cyclic vomiting syndrome attending a university-based practice were reviewed. Each had received zonisamide (median dose, 400 mg/d) or levetiracetam (median dose, 1000 mg/d) because tricyclic antidepressants alone were unsatisfactory as maintenance medications. Outcome was graded from chart review and directed interview; characteristics of the vomiting episodes were compared before and after initiation of antiepileptic drug therapy. RESULTS: At least moderate clinical response was described by 15 (75.0%) subjects, and 4 of these (20.0% of the total) reported symptomatic remission during 9.5 +/- 1.8 months of follow-up. Rate of vomiting episodes decreased from 1.3 +/- 0.3 to 0.5 +/- 0.2 per month (P = .01). Tricyclic antidepressants were discontinued in 11 (61.1%) of the 18 subjects who were still taking the medications when antiepileptic drug therapy was initiated. Moderate or severe side effects were reported by 45.0%, but by switching drugs, intolerance to antiepileptic drug therapy occurred in only 1 subject. CONCLUSIONS: Newer antiepileptic drugs, specifically zonisamide and levetiracetam, appeared beneficial as maintenance medications for nearly three fourths of adults with cyclic vomiting syndrome in this uncontrolled clinical experience. Although side effects occur in a large proportion of subjects, newer antiepileptic drugs might offer an alternative for patients who fail conventional treatment.

Adult↗
PubMed2006

Determination of zonisamide by a coated monolithic column.

In this paper, a monolithic ODS-silica gel column dynamically coated with cetylpyridinium chloride (CPC) was used to demonstrate the high-speed and efficient separation of zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS), its raw material (1,2-benzisoxazole-3-methanecarbonic acid) and intermediate (sodium 1,2-benzisoxazole-3-methanesulfonate) in drugs. Using a 40 mmol/L sodium perchlorate solution (pH 7.0) containing 10% acetonitrile as eluent, the analytes were eluted with a sharp and symmetrical peak within 3.0 min, detected with UV detection at 210 nm. The column demonstrates excellent stability over time, and exhibits unusual selectivity for pharmaceutical analysis. Thus, by this developed method, zonisamide in drug samples can be determined rapidly with high recoveries and good selectivity.

Anticonvulsants↗
PubMed1990

Determination of zonisamide (3-sulphamoylmethyl-1,2-benzisoxazole) in plasma at therapeutic concentrations by high-performance liquid chromatography.

A selective and sensitive liquid chromatographic method for the determination of zonisamide in small (0.1 ml) plasma samples is described. After adding internal standard, a direct solvent extract of the sample is examined by reversed-phase liquid chromatography with ultra-violet spectrophotometric detection. The method is rapid, simple and capable of determining plasma levels after therapeutic ingestion of zonisamide. Some results from a dose-ranging clinical trial are presented.

Anticonvulsants↗
PubMed2001

Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide.

The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75 mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were investigated. Nitric oxide production was obtained by measuring the combined level of nitrite plus nitrate (NOx). Zonisamide and PB dose-dependently suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels, ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines, while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the coadministration of two drugs on monoamines were similar to that of ZNS alone. These results suggest that one of the anticonvulsant effects of coadministration of PB and ZNS may be caused by changes in NOx levels.

Animals↗
PubMedDate not supplied

Drug monitoring and toxicology: a procedure for the monitoring of levetiracetam and zonisamide by HPLC-UV.

This article describes a rapid isocratic high-performance liquid chromatographic (HPLC) method for the simultaneous measurement of the anticonvulsants levetiracetam and zonisamide. Monitoring these drugs is important for detecting potentially toxic concentrations, particularly in patients with renal impairment, but no commercial assays are currently available. Following a liquid-liquid extraction, levetiracetam (5-150 microg/mL) and zonisamide (5-80 microg/mL) are quantitated by HPLC-UV. The assay's limit of quantitation, linearity, imprecision, and accuracy adequately cover the therapeutic range of these drugs. The assay should be attractive to clinical laboratories because the run time for quantification of both drugs is approximately 5 min per sample, and no interferences are currently known.

Anticonvulsants↗
PubMedDate not supplied

Pilot study of zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in patients with refractory partial seizures.

A new anticonvulsant compound, zonisamide (1,2 benzisoxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were higher than plasma concentrations because of red blood cell binding. Steady-state plasma concentrations were higher than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal systems were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day.

Adult↗
PubMed2004

Zonisamide treatment for symptomatic infantile spasms.

The authors evaluated zonisamide for symptomatic infantile spasms in 23 patients. Spasm cessation, EEG evolution, and tolerability were assessed for a mean duration of 6.5 months. Six patients (26%) had complete control with cessation of spasms and clearing of hypsarrhythmia. Mean latency time from onset of zonisamide treatment to complete spasm control was 19 days. There were no discontinuations due to adverse effects.

Anticonvulsants↗
PubMed2003

Influence of coadministered antiepileptic drugs on serum zonisamide concentrations in epileptic patients: quantitative analysis based on suitable transforming factor.

We conducted a study to clarify the most suitable transforming factor related to the daily zonisamide dose (D) providing a steady-state serum concentration (C(t)) and analyzed the influences of the concomitant use of antiepileptic drugs on C(t) quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 175 epileptic patients treated with the multiple oral administrations of zonisamide (ZNS) as a powder/tablets, were used for the analysis. Employing the extracellular water volume (V(ECW)) as a transforming factor, led the level/dose (L/D) ratio (:C(t)/(D/V(ECW))) to be independent of the patient's age and sex for the administration of ZNS alone. C(t) was revealed to be dependent on only one variable regarding D/V(ECW) and expressed as C(t)=0.604x(D/V(ECW)). Phenytoin (PHT) significantly lowered (p<0.01) the L/D ratio to 0.76 of the value for ZNS alone. For a more detailed analysis, we defined the parameter R(i) (i=1, 2, em leader, 6) as an alteration ratio, representing the influence of each antiepileptic drug on the L/D ratio of ZNS alone. A model based on the assumption that each R(i) value was independent from one another and multiplicative, was adopted. The analysis clarified that phenobarbital, valproic acid, carbamazepine, and PHT significantly lowered (p<0.05) the L/D ratio of ZNS to 0.849, 0.865, 0.846, and 0.804, respectively. In the case of the addition or discontinuance of concomitant treatment with antiepileptic drugs in the same patient, the estimated L/D ratios were calculated using the value of each R(i) and compared with the measured ones. The mean of prediction error was calculated as 22.9%. Our results appear valid and R(i) should be available for clinical use.

Administration, Oral↗
PubMed2003

Acute zonisamide overdose: a death revisited.

Overdose experience with the anti-epileptic agent zonisamide (Zonegran, ZNS) is limited. We present a case of suspected zonisamide overdose previously reported in abstract form, manifesting as seizures, dysrhythmias and death of an 18-y-o woman after single ingestion of 4.8 g ZNS in a suicide attempt. The patient experienced multiple generalized tonic-clonic seizures and copious airway secretions. En route to the emergency department, she sustained cardiopulmonary arrest from which she was resuscitated. CT scan of the head approximately 24 h after initial presentation revealed massive cerebral edema with tonsillar herniation; brain death was confirmed. Serum ZNS was 44 mg/L, and the case was officially deemed death secondary to ZNS overdose. Subsequently, a comprehensive urine drug screen demonstrated mirtazepine, diphenhydramine metabolites, and caffeine. Due to confounding factors, a definitive causal role for ZNS in this overdose death cannot be made, despite the county coroner's ruling.

Adolescent↗
PubMed2007

A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.

Medical therapy for essential tremor (ET), a common movement disorder, is often inadequate. We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide (ZNS), an antiepileptic agent, in treating ET. Twenty patients (mean age, 60 +/- 15 years) with ET were randomized to receive ZNS or placebo. ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale at baseline and days 14 and 28, as well as the Clinical Global Impression (CGI-C) scale at day 28. At endpoint, subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day. There were no significant improvements in the FTM total score or its subsections. Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline (-0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s(2); P = 0.03). On the CGI-C, 60% (n = 6) of patients in the ZNS group felt that their tremor was unchanged, while the remaining patients felt that their tremor was "minimally improved." Thirty percent (n = 3) of patients taking ZNS discontinued the study due to side effects (fatigue, headache, paresthesias) while taking 100 mg per day. ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated. ZNS was effective in reducing tremor amplitude as measured by accelerometry.

Anticonvulsants↗