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














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    abstract:OBJECTIVE:To clarify the clinical and neurophysiological profiles of fronto-parietal opercular epilepsy in which epileptic spikes are detected with magnetoencephalography (MEG) but not with scalp electroencephalography (EEG). METHODS:Four patients presented with epileptic spikes localized to the fronto-parietal opercu...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Kakisaka Y,Iwasaki M,Alexopoulos AV,Enatsu R,Jin K,Wang ZI,Mosher JC,Dubarry AS,Nair DR,Burgess RC

    更新日期:2012-11-01 00:00:00

  • Epilepsy beyond seizure: a population-based study of comorbidities.

    abstract::Comorbid conditions may affect the quality of life in persons with epilepsy (PWE) more than seizures. Using legally mandated healthcare encounter data, somatic, psychiatric, and neurodevelopmental comorbidities in a large population-based cohort of PWE, were compared to persons with migraine (PWM), a similar neurologi...

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    authors: Selassie AW,Wilson DA,Martz GU,Smith GG,Wagner JL,Wannamaker BB

    更新日期:2014-02-01 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...

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    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

  • 30 years of vagus nerve stimulation trials in epilepsy: Do we need neuromodulation-specific trial designs?

    abstract::Neuromodulation therapies represent an important treatment arm for patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery. Vagus nerve stimulation (VNS) - the neurostimulation modality in focus in this review - was the first available neuromodulatory therapy for DRE and was followed b...

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  • Metabolic and endocrine effects of valproic acid chronic treatment.

    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...

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    authors: Belcastro V,D'Egidio C,Striano P,Verrotti A

    更新日期:2013-11-01 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...

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    更新日期:2001-09-01 00:00:00

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    abstract::We examined 1715 seizures recorded on a dedicated epilepsy inpatient ward over 363 days in 2006-2007. Epileptic seizures, particularly complex partial seizures are less likely to occur on bright sunny days, than dull days. This correlation remains stable when seasonal patterns are controlled for. Non-epileptic attacks...

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    authors: Baxendale S

    更新日期:2009-03-01 00:00:00

  • Neural functional connectivity in patients with periventricular nodular heterotopia-mediated epilepsy.

    abstract::Periventricular nodular heterotopia (PNH) is characterized by disabled neural migration and is usually associated with epilepsy. Despite awareness of PNH-related epilepsy, little is known about the brain-level underlying functional neural bases. Thus, we used functional magnetic resonance imaging (MRI) to examine the ...

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    authors: Liu W,Yue Q,Tian Y,Gong Q,Zhou D,Wu X

    更新日期:2021-01-05 00:00:00

  • Validation of the Chinese version of the Liverpool Adverse Events Profile in patients with epilepsy.

    abstract::The objective of the study was to validate the Chinese version of The Liverpool Adverse Events Profile (LAEP) in patients with epilepsy. The scale was translated from the English version into a Chinese version and was then back-translated to examine its accuracy. Content validity, concurrent validity, and construct va...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Chen HF,Tsai YF,Shih MS,Chen JC

    更新日期:2011-03-01 00:00:00

  • SPM analysis of ictal-interictal SPECT in mesial temporal lobe epilepsy: relationships between ictal semiology and perfusion changes.

    abstract::A combination of temporo-limbic hyperperfusion and extratemporal hypoperfusion was observed during complex partial seizures (CPS) in temporal lobe epilepsy (TLE). To investigate the clinical correlate of perfusion changes in TLE, we analyzed focal seizures of increasing severity using voxel-based analysis of ictal SPE...

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    authors: Chassagnon S,Namer IJ,Armspach JP,Nehlig A,Kahane P,Kehrli P,Valenti MP,Hirsch E

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    pub_type: 杂志文章


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    abstract::The effects of GABA uptake inhibitors, SKF 89976A and SKF 100330A, on recurrent inhibition were studied in the rat hippocampal slice preparation by the antidromic-orthodromic stimulation test. Population spikes evoked orthodromically by stimulation of the stratum radiatum and recorded in the CA1 pyramidal cell body la...

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    authors: Capek R,Esplin B

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  • Effect of arterial blood pressure and serum glucose on brain intracellular pH, cerebral and cortical blood flow during status epilepticus in the white New Zealand rabbit.

    abstract::Generalized seizures can induce both hypertension and hyperglycemia which may aggravate preexisting cerebral or medical conditions in patients. In vivo fluorescent imaging of regional cortical blood flow and brain intracellular pH (pHi) was performed in fasted New Zealand rabbits (n = 35) in which either mean arterial...

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    authors: Tomlinson FH,Anderson RE,Meyer FB

    更新日期:1993-02-01 00:00:00

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    abstract::Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling ...

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    authors: Motamedi GK,Salazar P,Smith EL,Lesser RP,Webber WR,Ortinski PI,Vicini S,Rogawski MA

    更新日期:2006-08-01 00:00:00

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    更新日期:2015-10-01 00:00:00

  • Long-term prognosis of patients with Lennox--Gastaut syndrome in recent decades.

    abstract:PURPOSE:We investigated long term prognosis of Lennox-Gastaut syndrome (LGS) with active application of recent advanced treatment modalities such as ketogenic diet (KD) or epilepsy surgery (ES). METHODS:We retrospectively evaluated 68 patients with LGS, aged 18-35 years. We assessed seizure outcomes for a range of the...

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    authors: Kim HJ,Kim HD,Lee JS,Heo K,Kim DS,Kang HC

    更新日期:2015-02-01 00:00:00

  • The contribution of AMPA and NMDA receptors to graded bursting activity in the hippocampal CA1 region in an acute in vitro model of epilepsy.

    abstract::The AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA receptor antagonist 2-amino-5-phosphonovalerate (D-APV) were used to investigate the contribution of excitatory amino acid (EAA) receptors to graded bursting activity recorded in the CA1 region of the rat hippocampal slice followi...

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    更新日期:1992-07-01 00:00:00

  • Alterations in hippocampal voltage-gated calcium channel alpha 1 subunit expression patterns after kainate-induced status epilepticus in aging rats.

    abstract::Young adult and aged male Fisher 344 rats underwent kainate-induced convulsive status epilepticus (SE) for 4 h prior to sacrifice to determine potential aging-related differences in the effect of prolonged SE on the expression of hippocampal voltage-gated calcium channels (VGCCs). Immunohistochemistry was performed on...

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    authors: Kelly KM,Ikonomovic MD,Abrahamson EE,Kharlamov EA,Hentosz TM,Armstrong DM

    更新日期:2003-11-01 00:00:00

  • Correlation between cerebral perfusion and hyperventilation enhanced focal spiking activity.

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    authors: Marrosu F,Puligheddu M,Giagheddu M,Cossu G,Piga M

    更新日期:2000-06-01 00:00:00

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    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...

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    authors: Arya R,Aungaroon G,Zea Vera A,Horn PS,Byars AW,Greiner HM,Mangano FT,Holland KD

    更新日期:2018-02-01 00:00:00

  • Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy.

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    journal_title:Epilepsy research

    pub_type: 杂志文章,多中心研究


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    authors: de la Garza MA,Poldiak D,Shade R,Salinas FS,Papanastassiou AM,Szabó CÁ

    更新日期:2019-09-01 00:00:00

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    journal_title:Epilepsy research

    pub_type: 杂志文章,评审


    authors: Reddy DS

    更新日期:2009-07-01 00:00:00

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    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Quiske A,Helmstaedter C,Lux S,Elger CE

    更新日期:2000-04-01 00:00:00

  • Anticardiolipin and antinuclear antibodies in epilepsy--a population-based cross-sectional study.

    abstract::Increased prevalence of autoantibodies has been suggested in patients with epilepsy. This study determined the presence of autoantibodies in a representative cohort of 960 patients with epilepsy. The frequency of antinuclear antibodies (ANA), immunoglobulin G class anticardiolipin antibodies (aCL) and anti-B2-glycopro...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Ranua J,Luoma K,Peltola J,Haapala AM,Raitanen J,Auvinen A,Isojärvi J

    更新日期:2004-01-01 00:00:00