Abstract:
OBJECTIVE:Lamotrigine (LTG) is approved for monotherapy following withdrawal from enzyme-inducing antiepileptic drugs. LTG is also frequently used in combination with sodium valproate (VPA), and withdrawal to monotherapy in this setting is also frequently desirable. Given the known pharmacokinetic interaction between these two drugs, clinically relevant questions that should be answered include (1) at what dose and/or concentration of VPA does this interaction begin, and (2) at what dose of VPA does maximal inhibition occur. METHODS:LTG pharmacokinetics was evaluated using single-dose LTG (25 mg) given before and following low-dose VPA co-medication (125, 250, 375, 500 mg per day VPA) in healthy subjects. Serial blood samples were obtained over 120 h post-dose in order to calculate LTG kinetic parameters including area under the concentration-time curve, apparent oral clearance, elimination half-life and percent inhibition of LTG clearance at each dosage level of VPA. Pharmacodynamic modeling was used to calculate EC(50) values for this interaction. RESULTS:LTG pharmacokinetic parameters were evaluated in adult healthy female & male volunteers. Mean trough VPA concentrations at doses of 125, 250, 375 and 500 mg per day were 6.5, 13.9, 16.1 and 31.9 microg/ml, respectively. Maximal theoretical inhibition of LTG oral clearance by VPA is approximately 65%, with an EC50 concentration value of approximately 5.6 microg/ml of VPA. Mean inhibition of LTG oral clearance during concomitant treatment with VPA 125, 250, 375 and 500 mg per day was 30.8, 51.5, 52.8 and 50.3%, respectively. CONCLUSIONS:These data suggest that VPA inhibition of LTG clearance begins at very low VPA doses and concentrations. Importantly, maximal inhibition can be expected at VPA doses of approximately 500 mg per day, with the magnitude of inhibition diminishing at doses below this. These data provide useful information to develop a dosing algorithm to facilitate conversion to LTG monotherapy.
journal_name
Epilepsy Resjournal_title
Epilepsy researchauthors
Gidal BE,Sheth R,Parnell J,Maloney K,Sale Mdoi
10.1016/j.eplepsyres.2003.09.008subject
Has Abstractpub_date
2003-12-01 00:00:00pages
85-93issue
2-3eissn
0920-1211issn
1872-6844pii
S0920121103001803journal_volume
57pub_type
临床试验,杂志文章,随机对照试验abstract:BACKGROUND:People with epilepsy may experience an altered pattern of mortality due to cancer. We determined cancer mortality in two distinct populations with epilepsy: (i) an institutionalised cohort with severe epilepsy (SEC) and (ii) another cohort with presumed milder epilepsy (MEC). METHODS:Mortality data from 197...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2008.11.001
更新日期:2009-02-01 00:00:00
abstract::To further elucidate the inheritance pattern and range of phenotypic manifestations of benign familial temporal lobe epilepsy (FTLE), we report a large family recently identified in southern Italy. There were 8 patients (4 men), ranging in age from 31 to 68 years in three generations. One affected patient was deceased...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(99)00080-7
更新日期:2000-02-01 00:00:00
abstract::Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurologic inherited disease with heterogeneity. Autosomal dominant (AD) is the common inherited mode. There have been two loci mapped to 16 chromosome for PKD. However, no gene responsible for it has been identified so far. We collected 6 pedigrees from Chinese mainla...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2008.04.012
更新日期:2008-08-01 00:00:00
abstract:OBJECTIVE:To characterize, in adolescents aged 12-17, the pharmacokinetic (PK) profile of perampanel, the impact of intrinsic and extrinsic factors on PK, and the relationships between perampanel exposure and cognitive function, seizure frequency, and responder status. METHODS:Population PK analysis used plasma concen...
journal_title:Epilepsy research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.eplepsyres.2016.08.025
更新日期:2016-11-01 00:00:00
abstract:PURPOSE:To try to prove in patients with refractory symptomatic epilepsy due to early brain injury involving thalamus and complicated by CSWS the effects of the isolation of the injured hemisphere, performed with functional hemisperectomy, on epilepsy, namely on CSWS. METHODS:Full clinical follow-up before and after s...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2009.09.014
更新日期:2009-12-01 00:00:00
abstract::The ketogenic diet has been used to treat intractable epilepsy for many years, yet the mechanism(s) underlying its effectiveness have not been completely elucidated. However, emerging evidence indicates that the ketogenic diet may correct or otherwise alter a 'dystopic' gut microbiota that exhibits altered fecal micro...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2020.106409
更新日期:2020-10-01 00:00:00
abstract::Although treatment of epilepsy easily evolves into a situation of overtreatment, reversing the process can be difficult and time consuming. Benefits of reducing overtreatment may include a decrease in side effects, better seizure control, a simplification in the medication regimen, improved compliance, and reduced cos...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/s0920-1211(02)00185-7
更新日期:2002-11-01 00:00:00
abstract::Infantile spasms (IS) is a devastating epilepsy syndrome treated with adrenocorticotropic hormone (ACTH). To demonstrate the effects of adrenal dysfunction, adrenalectomy (ADX) and N-methyl-d-aspartate (NMDA)-induced rat model studies of IS were performed. The latency of the seizure in the ADX group decreased and the ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2012.02.001
更新日期:2012-06-01 00:00:00
abstract::Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resis...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2013.08.016
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to investigate whether there may be a correlation between the anatomical variants of Circle of Willis (CoW) and presence/laterality of mesial temporal sclerosis (MTS). METHODS:We retrospectively identified the CoW variants on Wada angiograms in 71 patients with pathologically proven...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2017.02.017
更新日期:2017-05-01 00:00:00
abstract:OBJECTIVE:Recent studies have suggested that the early introduction of a ketogenic diet (KD) could improve seizure control in myoclono-astatic epilepsy (MAE). This multicenter study sought to identify the benefits of KD use on seizure control and epilepsy and on developmental outcomes in children with resistant MAE. M...
journal_title:Epilepsy research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.eplepsyres.2017.02.005
更新日期:2017-03-01 00:00:00
abstract::The experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period...
journal_title:Epilepsy research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0920-1211(96)00031-9
更新日期:1996-11-01 00:00:00
abstract::Levetiracetam is a novel antiepileptic drug with an unknown mechanism of action. To-date levetiracetam is not known to be associated with any clinically significant pharmacokinetic interaction. Similarly, levetiracetam has not been associated with any pharmacodynamic interactions. We present four patients with severe ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(01)00309-6
更新日期:2002-02-01 00:00:00
abstract::Triheptanoin, the triglyceride of heptanoate, is used to treat certain hereditary metabolic diseases in USA because of its anaplerotic potential. In two chronic mouse seizure models this clear tasteless oil was found to be reproducibly anticonvulsant. Here we investigated the effects of triheptanoin feeding in C3H and...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2011.12.013
更新日期:2012-05-01 00:00:00
abstract::We retrospectively analyzed published studies to investigate historical trends in outcome of childhood absence epilepsy (CAE). We included patients based on onset of absence seizures in childhood, 3 Hz bilateral spike-wave discharges on EEG, and availability of seizure-free outcome data. The primary endpoint was seizu...
journal_title:Epilepsy research
pub_type: 历史文章,杂志文章,meta分析
doi:10.1016/j.eplepsyres.2019.02.013
更新日期:2019-05-01 00:00:00
abstract::The purpose of this investigation was to inquire into the multietiological determinants of psychopathology and social competence in children with epilepsy. The relationship between behavioral functioning as assessed by the Child Behavior Checklist and a variety of biological, psychosocial, medication and demographic r...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(88)90010-1
更新日期:1988-01-01 00:00:00
abstract::Hippocampal Deep Brain Stimulation (DBS) is proposed as an experimental treatment for refractory epilepsy, but the optimal stimulation parameters are undetermined. High frequency hippocampal DBS at 130Hz is effective in both animals and patients with epilepsy. Low frequency stimulation (approximately 5Hz) is assumed t...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2009.11.014
更新日期:2010-02-01 00:00:00
abstract::The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron e...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2014.09.013
更新日期:2014-12-01 00:00:00
abstract::Overexpression of multidrug efflux transporters such as P-glycoprotein (Pgp; ABCB1) or multidrug resistance proteins (MRPs; ABCC) in the blood-brain barrier has recently been suggested to explain, at least in part, pharmacoresistance in epilepsy, which affects about 30% of all patients with this common brain disorder....
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2003.12.007
更新日期:2004-02-01 00:00:00
abstract:OBJECTIVE:to determine the feasibility as well as the attitudes among caregivers of children and adolescents with epilepsy in China towards the use of smart phone applications (apps) for the management of seizures. METHODS:The caregivers of children and adolescents with epilepsy, ages ranging from 0 to 15 years, were ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2016.08.002
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Asymmetry of hippocampal internal architecture (HIA) clarity has been suggested to be a sign of hippocampal sclerosis (HS) and is frequently associated with other MRI findings of HS. The goal of this work is to use a previously developed HIA visual scoring system (Ver Hoef et al., 2013) to quantify HIA asymm...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2013.05.008
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:GRIN-related developmental-epileptic encephalopathies are associated with a spectrum of neurodevelopmental disorders, including intellectual disability, epilepsy including continuous spike-and-wave during sleep syndrome (CSWS), or epilepsy-aphasia spectrum phenotypes such as in Landau-Kleffner syndrome. Effi...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2020.106325
更新日期:2020-07-01 00:00:00
abstract:INTRODUCTION:Epilepsy surgery is an effective treatment for refractory focal epilepsy. Risks of surgery need to be considered when advising individuals of treatment options. We describe the frequency and nature of physical adverse events associated with epilepsy surgery in a single center. MATERIAL AND METHODS:We revi...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2017.02.016
更新日期:2017-05-01 00:00:00
abstract:AIM:Vitamin D (Vit D) has been considered as a neurosteroid and has a pivotal role in neuroprotection including epilepsy. Vit D regulator acts via a Vit D receptor (VDR). WAG/Rij rats have a genetically epileptic model of absence epilepsy with comorbidity of depression. The aim of the present study was to investigate t...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2019.106208
更新日期:2019-11-01 00:00:00
abstract:PURPOSE:Studies of adults who underwent temporal lobectomy for intractable temporal lobe epilepsy (TLE) demonstrated declining seizure free rates over time. Using seizure and social parameters, we followed patients who had temporal lobe surgery (TLS) in childhood to determine long-term outcomes. METHODS:We identified ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2008.07.012
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:In many parts of eastern Asia, rice is a dietary staple and therefore the ketogenic diet (KD) can be difficult to administer. The aim of this study was to assess the long-term effectiveness and tolerability of the classical KD using a 2:1 ratio of fat to protein plus net carbohydrates, which is lower than th...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/j.eplepsyres.2018.09.002
更新日期:2018-11-01 00:00:00
abstract::Dogs were treated with clorazepate, which is known to be completely metabolized to desmethyldiazepam. 2 mg/kg t.i.d. were given orally for 5-6 weeks, a dose regimen providing plasma concentrations of desmethyldiazepam in the range known to be therapeutic in man. The rate of development of tolerance to the anticonvulsa...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(89)90042-9
更新日期:1989-03-01 00:00:00
abstract::We report an interaction between lamotrigine (LTG), a new antiepileptic drug (AED), and carbamazepine (CBZ) and its primary metabolite CBZ-10,11-epoxide (CBZ-E) in 9 consecutive patients (5 male, 4 female, aged 19-31 years). After introduction of LTG (median daily dose 200 mg, range 100-300 mg) the mean serum CBZ-E co...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/0920-1211(92)90049-y
更新日期:1992-04-01 00:00:00
abstract::The characteristics of evoked potentials in patients with dentatorubral-pallidoluysian atrophy (DRPLA) were investigated. Twelve patients with DRPLA and three patients with progressive myoclonic epilepsy (PME) attributable to other causes participated in the study. In 11 out of the 12 patients, the diagnosis of DRPLA ...
journal_title:Epilepsy research
pub_type: 杂志文章
doi:10.1016/s0920-1211(99)00028-5
更新日期:1999-10-01 00:00:00
abstract::Benign myoclonic epilepsy in infancy is a rare syndrome with just over 100 cases reported since the first syndromic description by Dravet and Bureau [Dravet, C., Bureau, M., 1981. The benign myoclonic epilepsy of infancy. Rev. Elecroencephalogr. Neurophysiol. Clin. 11, 438-444]. This includes 23 infants with reflex my...
journal_title:Epilepsy research
pub_type: 杂志文章,评审
doi:10.1016/j.eplepsyres.2006.01.014
更新日期:2006-08-01 00:00:00