The influence of old age and enzyme inducing comedication on the pharmacokinetics of valproic acid at steady-state: A case-matched evaluation based on therapeutic drug monitoring data.


PURPOSE:To evaluate the influence of aging on the pharmacokinetics of valproic acid (VPA) at steady-state and on the susceptibility of VPA metabolism to enzyme induction by antiepileptic comedication. METHODS:The database of the therapeutic drug monitoring service of a large neurological hospital was searched to identify patients aged > or = 65 years stabilized on VPA therapy. Apparent VPA oral clearance (CL/F) calculated for each elderly patient was compared with that determined in an equal number of VPA-treated controls aged 20-50 years and matched for gender, body weight and antiepileptic drug (AED) comedication. RESULTS:A total of 71 elderly patients aged 70.0+/-4.4 years, including 20 receiving enzyme inducing AEDs, was included in the main evaluation. In the absence of enzyme inducing comedication, VPA CL/F in the elderly was similar to that found in non-elderly controls (9.7+/-4.6 versus 10.2+/-4.6mlh(-1)kg(-1)). Elderly patients on enzyme inducing comedication, on the other hand, had lower CL/F values than enzyme induced younger controls (11.7+/-5.4 versus 16.0+/-6.3mlh(-1)kg(-1), p<0.05). Since VPA CL/F is known to increase with increasing dosage, a lower VPA dosage in elderly patients comedicated with enzyme inducers compared with controls may have contributed to differences in CL/F between the two groups. CONCLUSIONS:In the absence of enzyme inducing comedication, VPA clearance in the elderly was comparable to that observed in controls. VPA clearance in elderly patients receiving enzyme inducing AEDs was lower than in controls, the difference being probably due to an influence of age as well as to the fact that mean VPA dosage was lower in these patients than in controls. Since our measurements of clearance were based on total serum VPA concentrations and VPA binding to plasma proteins is known to be reduced in old age, it is likely that the clearance of unbound, pharmacologically active, VPA was decreased to an important extent in the elderly, presumably as a result of a decline in drug metabolizing capacity.


Epilepsy Res


Epilepsy research


Fattore C,Messina S,Battino D,Croci D,Mamoli D,Perucca E




Has Abstract


2006-08-01 00:00:00














  • Visual seizures in children.

    abstract::Twenty-one children (11 boys, 10 girls) suffering from visual seizures were studied. The visual seizures manifested as loss of vision, flickering light, blurring or figurative hallucinations. Ictal EEGs during visual seizures were recorded in 4 cases; the ictal discharges all originated in the occipital area. Visual s...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Aso K,Watanabe K,Negoro T,Takaesu E,Furune A,Takahashi I,Yamamoto N,Nomura K

    更新日期:1987-07-01 00:00:00

  • Optimised interictal HMPAO-SPECT in the evaluation of partial epilepsies.

    abstract::Interictal blood flow single photon emission computed tomography (SPECT) has been considered to be of limited value in the investigation of patients with partial epilepsies. Newer SPECT technologies using brain dedicated multiple detector systems have not been fully evaluated. To study the usefulness of an optimized S...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Schmitz EB,Costa DC,Jackson GD,Moriarty J,Duncan JS,Trimble MR,Ell PJ

    更新日期:1995-06-01 00:00:00

  • Efficacy of a ketogenic diet in resistant myoclono-astatic epilepsy: A French multicenter retrospective study.

    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


    authors: Stenger E,Schaeffer M,Cances C,Motte J,Auvin S,Ville D,Maurey H,Nabbout R,de Saint-Martin A

    更新日期:2017-03-01 00:00:00

  • Exposure of hippocampal slices to magnesium-free medium produces epileptiform activity and simultaneously decreases calcium and calmodulin-dependent protein kinase II activity.

    abstract::The effect of magnesium-free medium on electrical and CaM kinase II activity in the rat hippocampal slice was examined. Experimental slices were incubated in 2 mM Mg, then exposed to magnesium-free medium for 1 h. Control slices were concurrently run in 2 mM Mg. Slices were then frozen and CaM kinase II activity was m...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Churn SB,Anderson WW,DeLorenzo RJ

    更新日期:1991-09-01 00:00:00

  • Role of choroid plexus epithelium in the removal of valproic acid from the central nervous system.

    abstract::Previous experiments suggest the primary route of valproic acid (VPA) removal from the rabbit central nervous system (CNS) is by probenecid-sensitive transporters at the blood-brain barrier but not at the choroid plexus. The purpose of this study was to determine if other transport mechanisms at the choroid plexus pla...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Adkison KD,Artru AA,Powers KM,Nochlin D,Shen DD

    更新日期:1995-03-01 00:00:00

  • Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone.

    abstract::Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Walton NY,Treiman DM

    更新日期:1988-03-01 00:00:00

  • Mutual interaction between remacemide hydrochloride and phenytoin.

    abstract::A randomised, double-blind, placebo-controlled crossover study of add-on remacemide hydrochloride was carried out in epilepsy patients being treated with phenytoin (PHT) monotherapy. Eleven patients were recruited, ten of whom completed the study. Plasma concentration profiles of PHT, remacemide, and its active desgly...

    journal_title:Epilepsy research

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Leach JP,Girvan J,Jamieson V,Jones T,Richens A,Brodie MJ

    更新日期:1997-01-01 00:00:00

  • The hippocampus participates in a pharmacological rat model of absence seizures.

    abstract:OBJECTIVE:Using the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if 2.5-6 Hz paroxysmal discharges (PDs) induced by GBL were synchronized among the thalamocortical system and the hippocampus, and whether inactivation of the hippocampus affected PDs. METHODS:Local fiel...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Arcaro J,Ma J,Chu L,Kuo M,Mirsattari SM,Stan Leung L

    更新日期:2016-02-01 00:00:00

  • Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy.

    abstract:UNLABELLED:Gabapentin (GBP) is a non-metabolized antiepileptic drug that is eliminated by renal excretion and displays saturable, dose dependent absorption. The recommended dosing schedule for GBP is t.i.d. At large daily doses, oral bioavailability (F) may be improved by giving the daily dose more frequently. OBJECTI...

    journal_title:Epilepsy research

    pub_type: 临床试验,杂志文章


    authors: Gidal BE,DeCerce J,Bockbrader HN,Gonzalez J,Kruger S,Pitterle ME,Rutecki P,Ramsay RE

    更新日期:1998-07-01 00:00:00

  • Amygdaloid kindling in brainstem bisected cats.

    abstract::Results of previous studies suggested that the brainstem participates in amygdaloid (AM) kindled seizure generalization and the positive transfer effect at the secondary site AM. This study was undertaken to define the role of the brainstem in the patterning of AM kindling, the maintenance of AM kindled seizure and th...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Hamada K,Wada JA

    更新日期:1998-01-01 00:00:00

  • Newly-diagnosed pediatric epilepsy is associated with elevated autoantibodies to glutamic acid decarboxylase but not cardiolipin.

    abstract::Glutamic acid decarboxylase autoantibodies (GADA) and anti-cardiolipin autoantibodies (ACA) have been detected in adult subjects with epilepsy, though the functional implications of these findings are a matter of debate. This study aimed to determine the prevalence of GADA and ACA and to investigate their clinical sig...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Veri K,Uibo O,Talvik T,Talvik I,Metsküla K,Napa A,Vaher U,Õiglane-Šlik E,Rein R,Kolk A,Traat A,Uibo R

    更新日期:2013-07-01 00:00:00

  • Comparison of PET measurements of cerebral blood flow and glucose metabolism for the localization of human epileptic foci.

    abstract::We compared the relative sensitivity of two interictal PET techniques, bolus injection of [15O] labeled water for estimation of cerebral blood flow (H2(15)O CBF-PET), and 18F 2-deoxyglucose (18FDG-PET) for cerebral glucose metabolism (CMRglc), and T2-weighted magnetic resonance imaging, in 28 patients with medically i...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Leiderman DB,Balish M,Sato S,Kufta C,Reeves P,Gaillard WD,Theodore WH

    更新日期:1992-11-01 00:00:00

  • Neurodevelopmental and epilepsy outcome in children aged one to five years with infantile spasms--a North Indian cohort.

    abstract:PURPOSE:The present study was planned as there is paucity of outcome data of children with infantile spasms, from India where profile of patients is different from the western world. Moreover, most previous studies have either not used strict inclusion criteria or standardized psychometric tests for developmental outco...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Sehgal R,Gulati S,Sapra S,Tripathi M,Kabra M,Pandey RM

    更新日期:2014-03-01 00:00:00

  • Genetic seizure susceptibility underlying acute encephalopathies in childhood.

    abstract::We herein investigated risk factors of pediatric acute encephalopathy (AE) regarding the hitherto uncharacterized genetic background of seizure susceptibility underlying the pathogenesis of AE. The study included 15 patients with a history of various types of AE in childhood. We undertook the mutational analysis of th...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Kobayashi K,Ouchida M,Okumura A,Maegaki Y,Nishiyama I,Matsui H,Ohtsuka Y,Ohmori I

    更新日期:2010-10-01 00:00:00

  • Life-threatening adverse events of antiepileptic drugs.

    abstract::Treating a patient with antiepileptic drugs (AEDs) may give rise to unexpected life-threatening adverse events. Despite extensive experimental and clinical testing to ensure safety, most AEDs on the market have been associated with cases of severe cutaneous reactions, serious hematological disorders, or hepatic failur...

    journal_title:Epilepsy research

    pub_type: 杂志文章,评审


    authors: Arroyo S,de la Morena A

    更新日期:2001-11-01 00:00:00

  • Dynamic magnetic source imaging of absence seizure initialization and propagation: a magnetoencephalography study.

    abstract:PURPOSE:The present study aims to determine the initialization and propagation of typical absence seizures using magnetoencephalography (MEG). METHOD:Fourteen drug-naïve children with childhood absence epilepsy (CAE) were studied using a 275-Channel MEG system. The spectral signatures of epileptic activity were assess...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Miao A,Tang L,Xiang J,Guan Q,Ge H,Liu H,Wu T,Chen Q,Yang L,Lu X,Hu Z,Wang X

    更新日期:2014-03-01 00:00:00

  • Lack of benefit of linoleic and alpha-linolenic polyunsaturated fatty acids on seizure latency, duration, severity or incidence in rats.

    abstract:BACKGROUND:Polyunsaturated fatty acids have been reported to increase seizure threshold and to reduce seizure duration and severity in rats. OBJECTIVE:The purpose of the present study was to test the anticonvulsant effects of an essential fatty acid mixture containing linoleic and alpha-linolenic acids at a 4:1 ratio ...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Taha AY,Baghiu BM,Lui R,Nylen K,Ma DW,Burnham WM

    更新日期:2006-09-01 00:00:00

  • Familial pure paroxysmal kinesigenic dyskinesia in Han population from the Chinese mainland: a new subtype?

    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


    authors: Zhou J,Li G,Chen C,Liu D,Xiao B

    更新日期:2008-08-01 00:00:00

  • Genetic and clinical features of SCN8A developmental and epileptic encephalopathy.

    abstract:OBJECTIVE:We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. METHODS:Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patie...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Kim HJ,Yang D,Kim SH,Kim B,Kim HD,Lee JS,Choi JR,Lee ST,Kang HC

    更新日期:2019-12-01 00:00:00

  • Ischaemic stroke in adults and epilepsy.

    abstract::Stroke is an important cause of symptomatic epilepsy especially in the elderly. Seizures in the setting of stroke will furthermore worsen the prognosis of stroke. Studies show that the frequency of seizures in stroke ranges between 2.3% and 14%. Typically early seizures are defined as those that occur within 14 days o...

    journal_title:Epilepsy research

    pub_type: 杂志文章,评审


    authors: Menon B,Shorvon SD

    更新日期:2009-11-01 00:00:00

  • Differences in evoked potential characteristics between DRPLA patients and patients with progressive myoclonic epilepsy: preliminary findings indicating usefulness for differential diagnosis.

    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


    authors: Kasai K,Onuma T,Kato M,Kato T,Takeya J,Sekimoto M,Watanabe K,Minami N,Goto Y,Minabe Y

    更新日期:1999-10-01 00:00:00

  • Acute psychological disorders in patients with epilepsy: a nation-wide study.

    abstract::Acute psychological disorders (APDs) are more common in epilepsy than in the general population, with estimates varying from 2 to 16% depending on the population of patients sampled. APD has traditionally been classified by seizure activity (ictal), the early post-ictal period (post-ictal) and unrelated to seizure act...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Cockerell OC,Moriarty J,Trimble M,Sander JW,Shorvon SD

    更新日期:1996-10-01 00:00:00

  • Grammar tests increase the ability to lateralize language function in the Wada test.

    abstract:INTRODUCTION:Grammar is a core component of the language system, yet it is rarely assessed during the Wada (intracarotid amobarbital) test. It is hypothesized that adding grammar tests to the recovery phase of the Wada test will increase our ability to lateralize language function. METHOD:Sixteen individuals (nine fem...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Połczyńska M,Curtiss S,Walshaw P,Siddarth P,Benjamin C,Moseley BD,Vigil C,Jones M,Eliashiv D,Bookheimer S

    更新日期:2014-12-01 00:00:00

  • Long-term observations of two siblings with Lafora disease treated with zonisamide.

    abstract::We have reported long-term clinical follow-up for two siblings with Lafora disease, a brother and sister, one of whom autopsied. Both siblings had repeated attacks of severe myoclonus, tonic and tonic-clonic convulsions, and intractable status epilepticus. The addition of orally administered zonisamide brought about s...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Yoshimura I,Kaneko S,Yoshimura N,Murakami T

    更新日期:2001-09-01 00:00:00

  • Allopregnanolone augments epileptiform activity of an in-vitro mouse hippocampal preparation in the first postnatal week.

    abstract::In the immature brain the neurotransmitter γ-amino butyric acid (GABA) mediates a membrane depolarization and can contribute to both, inhibition and excitation. Therefore the consequences of a positive modulation of GABA(A) receptors by neurosteroids on epileptiform activity are hard to predict. In order to analyze wh...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Sharopov S,Winkler P,Uehara R,Lombardi A,Halbhuber L,Okabe A,Luhmann HJ,Kilb W

    更新日期:2019-11-01 00:00:00

  • Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development.

    abstract::Clinical and epidemiological studies have repeatedly demonstrated that a subset of patients with epilepsy have progressive syndromes with increasing seizure frequency and cumulative adverse effects despite optimal anticonvulsant therapy. Recent longitudinal imaging studies and long-term neuropsychological studies have...

    journal_title:Epilepsy research

    pub_type: 杂志文章,评审


    authors: Sutula TP

    更新日期:2004-07-01 00:00:00

  • Polyamine metabolism in epileptic cortex.

    abstract::Polyamine (tissue) concentrations have been studied in hippocampus and temporal neocortex from patients with temporal lobe epilepsy. Depth electrode recordings demonstrated hippocampal origin of the seizures, the temporal neocortex being involved during the discharge propagation. Neuropathological examination of excis...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Laschet J,Trottier S,Grisar T,Leviel V

    更新日期:1992-07-01 00:00:00

  • Long-term decrease in Na+,K+-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit.

    abstract::Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na(+),K(+)-ATPase activity contributes to the maintenance ...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Funck VR,Ribeiro LR,Pereira LM,de Oliveira CV,Grigoletto J,Fighera MR,Royes LF,Furian AF,Oliveira MS

    更新日期:2014-12-01 00:00:00

  • Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients.

    abstract::Controversy exists as to whether hippocampal sclerosis (HS) is a preexisting cause or a consequence of seizures. We investigated 122 consecutive patients who underwent anterior temporal lobectomy for intractable epilepsy between 1989 and 1992. MRI scans were normal apart from evidence of HS in 5 cases. The degree of H...

    journal_title:Epilepsy research

    pub_type: 临床试验,杂志文章


    authors: Davies KG,Hermann BP,Dohan FC Jr,Foley KT,Bush AJ,Wyler AR

    更新日期:1996-06-01 00:00:00

  • Increased neocortical spiking and surgical outcome after selective amygdalo-hippocampectomy.

    abstract::We studied the electrocorticogram (ECoG) before and immediately after transcortical selective amygdalo-hippocampectomy, prospectively in 13 consecutive patients and retrospectively in three others. ECoG was performed with surface and two depth electrodes inserted through T2 aimed at the amygdala and anterior hippocamp...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Cendes F,Dubeau F,Olivier A,Cukiert A,Andermann E,Quesney LF,Andermann F

    更新日期:1993-12-01 00:00:00