Liquid chromatographic methods for determination of the new antiepileptic drugs stiripentol,retigabine,rufinamide and perampanel:A comprehensive and critical review / 药物分析学报

The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic (LC) methods coupled with ultraviolet,fluores-cence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chro-matographic methods developed for the analysis of perampanel,retigabine (and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new (bio)analytical techniques are aimed to be imnlemented for these drugs.

Rufinamide in Patients with Childhood Onset Intractable Epilepsy / 대한소아신경학회지

PURPOSE: This study is aimed to evaluate the effectiveness and tolerability of rufinamide as add-on therapy in patients with intractable epilepsies. METHODS: We retrospectively reviewed the medical records of 70 patients treated with rufinamide in Asan Medical Center, children's hospital. Two cases with incomplete medical records were excluded and total sixty-eight cases were enrolled. Rufinamide was added on the existing antiepileptic drugs and the total seizure frequency at pre-medication, 3 months and 12 months were examined. RESULTS: The mean age of 68 patients (43 male) was 10.5 yrs (range, 1-24 yrs). At 3 months after rufinamide initiation, 5 patients achieved freedom from seizures and 28 (41.2%) achieved a ≥50% seizure reduction. At 12 months, 7 patients achieved seizure freedom and 29 (42.6%) achieved ≥50% seizure reduction. The retention rate was hold up to 75.0% at 3 months and 66.2% at 12 months of study. Total 29 patients reported adverse events in order of seizure aggravation, somnolence, insomnia, common cold, nausea and vomiting. CONCLUSION: In this study, rufinamide is effective and tolerable in patients with other intractable epilepsy of childhood onset as well as the patients with LGS. Further research is required to define the efficacy of rufinamide in intractable epilepsy other than LGS.

Effectiveness and Tolerability of Rufinamide in Korean Children with Lennox-Gastaut Syndrome / 대한소아신경학회지

PURPOSE: Rufinamide (RFM) is known to be effective for children with Lennox-Gastaut syndrome (LGS). The aim of this study is to evaluate its efficacy and tolerability of Korean children with LGS. METHODS: This is a single center, open label, retrospective study. Patients with LGS who received rufinamide as adjunctive therapy were enrolled in this study. Their baseline clinical characteristics, the percent change in the seizure frequency per 4 weeks, and adverse events were evaluated. RESULTS: Among 32 children, 20 were males and the mean age was 11.3±6.6 years. After 1 month of rufinamide medication, the frequency of seizures was reduced by more than 50% in 31.3% of patients and 6.3% of patients had no seizures. After 6 months of rufinamide administration, patients with a 50% or less decrease in seizure frequency remained in a state of reduced seizure frequency and 3.1% of patients had no seizures. Side effects such as nausea, vomiting, anorexia, less active, somnolence, aggression, drooling were noted in 28.1% of patients. CONCLUSION: This study suggests that rufinamide can be considered as an effective and safe treatment option for intractable epileptic children such as LGS.

Rufinamide: treatment of seizures associated with Lennox–Gastaut syndrome.

Rufinamide (RUF) is FDA-approved for adjunctive management of seizures related with Lennox–Gastaut syndrome (LGS). This new anti-epileptic drug (AED) adds to the AEDs previously used for LGS together with valproic acid, lamotrigine, felbamate, and topiramate. Its mechanism of action includes preventive the excessive firing of sodium-dependent action potentials, but RUF also exhibits a broad spectrum of action in animal models. The plasma concentration of other AEDs does not change by the RUF. Dizziness, nausea, diplopia, and ataxia vomiting and somnolence are most common adverse effects taking place with RUF. Status epilepticus has been reported, but were uncommon (0.9%). A recent randomized, double-blinded, placebo-controlled trial of RUF in patients with LGS and generalized seizures, including atypical absence and tonic-atonic seizures, showed a 32.7% median percentage decreased in total seizures and a 42.5% median percentage decreased in tonic-atonic seizures. RUF also considerably decreased seizure severity. RUF has been studied as adjunctive therapy for partial seizures in adults and adolescents. In a study of three healthy volunteers, an oral dose of 600 mg RUF recognized high absorption and monoexponential elimination with a mean half-life (t½) of 9 hrs. Excretion was mainly renal (85%) and complete (98%) within 7 days.

Efficacy and Tolerability of Rufinamide for Intractable Generalized Epilepsies / 대한소아신경학회지

PURPOSE: The purpose of the study was to evaluate the efficacy and safety of rufinamide for intractable generalized epilepsies. METHODS: Eighteen patients with intractable generalized epilepsies were included in the study. Their medical records were retrospectively reviewed. Rufinamide was administered as an add-on treatment for intractable epilepsies. The initial administered dose was 10 mg/kg/day, which was subsequently titrated up to 30-50 mg/kg/day. The effectiveness was assessed by comparing the frequency of seizures after the treatment. The difference in number of seizures during 4 weeks was compared before and after reaching the final dose. RESULTS: The study population consisted of 13 males and 5 females (mean age 13.6+/-6.2 years, range 3.3-29.2 years). The responder rate (> or =50% in seizure frequency) was 39% and the seizure free rate was 11%. Retention rate was 44% and the reasons for withdrawal was adverse events (6/18 patients, 33%), aggravation of seizures (4/18 patients, 22%), and ineffectiveness (2/18 patients, 11%). Adverse events included hyperactivity, somnolence, ataxia and polyhidrosis. Adverse events and seizure aggravation occurred even at the starting dose of rufinamide treatment. CONCLUSION: Rufinamide can be used as an efficacious and safe adjunctive anticonvulsant for patients with intractable generalized epilepsy.

Droga órfã: surgimento de um novo conceito / Orphan drug: arisement of new concept

INTRODUÇÃO: A partir de 2007, quatro novas drogas anti-epilépticas foram aprovadas, o acetato de eslicarbazepina, lacosamida, rufinamida e estiripentol. Destas drogas, duas aparecem como drogas órfãs, ou seja, drogas desenvolvidas especificamente para o tratamento de uma síndrome-específica, sendo essas, o estiripentol, indicada na Síndrome de Dravet e a rufinamida, na Síndrome de Lennox-Gastaut. OBJETIVO: Revisar a eficácia, tolerabilidade e efeitos adversos das novas drogas, em especial das drogas órfãs. MÉTODO: Estudos foram selecionados de banco de dados eletrônicos. A análise destes estudos averiguou a eficácia, efetividade, efeitos adversos mais comuns, raros e de longo prazo assim como a comparação com os fármacos existentes. CONCLUSÕES: O desenvolvimento de drogas específicas no tratamento das síndromes epilépticas constitui-se na pedra angular do tratamento da epilepsia, minimizando o tempo até o alcance do controle de crises, com consequente menor tempo de exposição aos efeitos deletérios da epilepsia.

INTRODUCTION: Four new antiepileptic drugs have been approved since 2007, eslicarbazepine acetate, lacosamide, rufinamide and stiripentol. Out of these, two drugs are orphan drugs, that is, drugs specifically designed for the treatment of a specific epileptic syndrome, such as stiripentol for Dravet Syndrome and rufinamide for Lennox-Gastaut Syndrome. OBJECTIVE: to review the efficacy, tolerability and adverse effects of the newly released drugs, especially of both orphan drugs. METHODOLOGY: Studies were selected from electronic data base. Analyses of these studies ascertained the most common, rare and long-term adverse effects, efficacy, and effectiveness, as well as comparison with existing drugs. CONCLUSIONS: The development of specific drugs in the treatment of epileptic syndromes constitutes the cornerstone in the treatment of epilepsy, minimizing the time needed to achieve seizure control, with consequent reduced exposure to the deleterious effects of epilepsy.