ABSTRACT
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.
ABSTRACT
OBJECTIVE：To establish a method for de termining stiripentol （STP）concentration in plasma and brain of rats ， and to compare the concentrations of STP and its self-nanoemulsifying drug delivery system （STP-SNEDDS）in plasma and brain. METHODS：Using xanthone as internal standard ，HPLC-fluorescence（HPLC-FLR）method was adopted. The determination was performed on Diamonsil C 18 column with mobile phase consisted of acetonitrile- 25 mmol/L KH 2PO4 solution [ 44 ∶ 56（V/V），pH 2.6] at a flow rate of 1.5 mL/min；the excitation and emission wavelengths were 210 nm and 400 nm，respectively；the column temperature was 30 ℃；the sample size was 10 μL. Totally 36 rats were randomly divided into 2 groups，with 18 rats in each group. They were given STP-SNEDDS and STP suspension （40 mg/kg，by STP ）intragastrically. Blood and brain tissue samples were collected at 0.5，1，2 h after administration （6 rats in each group at different time point ）. After the protein was precipitated by acetonitrile （brain tissue should be homogenized ），the concentrations of STP were determined by the above chromatographic conditions. RESULTS ：The linear ranges of STP concentration in plasma and brain tissue were 0.02-8.00 μg/mL（r were 0.999 6， 0.999 4，respectively）. The limits of quantitation were both 0.02 μg/mL. The inter-day and intra-day RSDs were all less than 5％. The extraction recovery and method recovery were all no less than 90％. Compared with STP suspension group ，the plasma concentration（except for 1 h after administration ）and cerebral concentration （except for 2 h after administration ）of STP in STP-SNEDDS group were all significantly increased （P＜0.05），showing significant linear relationship between them （for STP-SNEDDS）. CONCLUSIONS ：Established HPLC-FLR method presents high accuracy and precision ，and can be used for the distribution of STP and STP-SNEDDS in plasma and brain.The concentration of STP in plasma and brain tissue isincreased after STP is made into SNEDDS.
ABSTRACT
Dravet syndrome ( DS) , known as severe myoclonic epilepsy of infancy, is a devastating disorder characterized by intractable epilepsy and poor neurodevelopmental outcome. Seizures are refractory to conventional antiepileptic therapy, therefore resulting in heavy psychological pressure and burden. Stiripentol ( STP) is a novel antiepileptic drug, which has been proposed to achieve better seizure control in DS. It acts as a direct GABA receptor agonist by increasing the GABAergic transmission and by prolongating the opening peri-od of the receptor dependent chloride channels. In addition, STP inhibits several isoenzymes of the cytochrome P450 system in the liver involved in the metabolism of other antiepileptics, thus potentiating their effects. By summarizing the relevant researches at home and abroad, we describe an on-going work in the anticonvulsant mechanisms and efficacy of STP, to provide an alternative treatment of DS.
ABSTRACT
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.