Plasma concentrations of vigabatrin in epileptic patients

Sánchez-Alcaraz, A.; Quintana, B de la; Rodríguez, I. Marcelino; López, Emilio Cuesta

doi:10.1111/j.1365-2710.1996.tb00037.x

Cited by 16 publications

(12 citation statements)

References 11 publications

(4 reference statements)

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“…It has been suggested that since vigabatrin is mainly eliminated renally (Schechter, 1989;Battino et al, 1995), the maturation of the rat kidney following birth will result in increased clearance and thus decreased exposure as the rat grows older. When administering vigabatrin to epileptic patients with complex partial seizures the mean plasma concentration of vigabatrin was found to be 42,000 ng/ml (Sá nchez-Alcaraz et al, 1996) and vigabatrin plasma C max values of approximately 65,000 ng/ml have been recorded in young children following administration of 50 mg/kg (Battino et al, 1995), although children approximately 1 year of age had somewhat lower plasma Cmax values of approximately 35,000 ng/ml. The high dose of 50 mg/kg/day used in this study thus results in rat plasma concentrations comparable to those seen in both juvenile and adult humans administered vigabatrin.…”

Section: Discussionmentioning

confidence: 95%

Vigabatrin-induced CNS changes in juvenile rats: Induction, progression and recovery of myelin-related changes

Rasmussen

Richmond²,

Wegener

et al. 2015

NeuroToxicology

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Section: Discussionmentioning

confidence: 95%

Vigabatrin-induced CNS changes in juvenile rats: Induction, progression and recovery of myelin-related changes

Rasmussen

Richmond²,

Wegener

et al. 2015

NeuroToxicology

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“…This activity is resistant to classic AEDs. Among newer AEDs, a similar effect was seen only with 5 mM VGB after 60-min application (data not published), a concentration much is clearly above plasma levels observed during treatment (26)(27)(28). The LRDs are also sen-sitive to NMDA-receptor antagonists such as ketamine, 2-amino-phosphonovaleric acid (APV), and dextrometorphan but not to antagonists that act on AMPAIkainate type of glutamate receptors (15,18,29,30).…”

Section: Discussionmentioning

confidence: 95%

Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices

Armand

Rundfeldt²,

Heinemann

2000

Epilepsia

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Summary:Purpose: The objective of this study was to evaluate the effect of a new antiseizure drug, retigabine (D-23129; N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid ethyl ester) on low-Mg*+-induced epileptiform discharges in rat in vitro.Methods: Three types of epileptiform discharges (recurrent short discharges in the hippocampus, seizure-like events, and late recurrent discharges in the entorhinal cortex) were elicited in rat combined entorhinal cortex-hippocampal slices by perfusion with low-Mg*+-artificial cerebrospinal fluid (ACSF). The antiepileptic properties of retigabine were evaluated as effect on the frequency and amplitude of the epileptiform activities as well as time of onset of the effect in the entorhinal cortex (EC) and in hippocampal area CAI (CAI) by using extracellular recording techniques.Results: Retigabine (20 pMj reversibly suppressed the recurrent short discharges otherwise sensitive only to high doses of valproate (VPA) but insensitive to standard antiepileptic drugs (AEDs) in CAI, whereas 10 pM reduced the frequency of discharges by 34 * 18.8%, with no significant effect on the amplitude. In EC, retigabine (50 p M ) reversibly suppressed the seizure-like events, whereas 20 blocked seizure-like events in 71.5% of the slices. The seizure-like events were also sensitive to standard AEDs. Late recurrent discharges in EC that are not blocked by standard AEDs were reversibly suppressed by retigabine (100 pMj, whereas 50 p M reduced the frequency of the discharges by 94.4 c 7.7%, and 20 pM, by 74.2 18.0%, with no significant effect on the amplitude.Conclusions: Retigabine is an effective AED with suppressive effects on recurrent short discharges and on late recurrent discharges normally insensitive to standard AEDs. Key Words: Retigabine-Epileptiform activities-Entorhinal cortex-Hippocampus-Low magnesium.Retigabine (D-23 129), a new antiseizure drug synthesized by ASTA Medica AG (Frankfurt, Germany), is a desazo analogue derivative of flupirtine. Retigabine has been shown to be an effective compound in a large variety of seizure models in vivo and in vitro (1). Retigabine is effective against maximal electroshock and subcutaneous pentylenetetrazol seizures (2,3), in the amygdala kindling model in rats (4), and in two genetic models of epilepsy, the audiogenic seizure DBA/2J mice and the genetically epilepsy-prone rats (5,6). In vitro, reti-

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“…Specifically, vigabatrin has been reported to decrease both pentobarbital and phenytoin drug concentrations [20,23]. Vigabatrin has also been reported to increase carbamazepine clearance [77].…”

Section: Drug Interactionsmentioning

confidence: 98%

Vigabatrin: a comprehensive review of drug properties including clinical updates following recent FDA approval

Tolman

Faulkner

2009

Expert Opinion on Pharmacotherapy

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Plasma concentrations of vigabatrin in epileptic patients

Abstract: Vigabatrin plasma levels show wide interpatient variability, and co-administration with carbamazepine increases vigabatrin's clearance. While there is no relationship between plasma level and anti-epileptic effect, abnormally high levels of the drug may increase toxicity.

Cited by 16 publications

References 11 publications

Vigabatrin-induced CNS changes in juvenile rats: Induction, progression and recovery of myelin-related changes

Vigabatrin-induced CNS changes in juvenile rats: Induction, progression and recovery of myelin-related changes

Effects of Retigabine (D‐23129) on Different Patterns of Epileptiform Activity Induced by Low Magnesium in Rat Entorhinal Cortex Hippocampal Slices

Vigabatrin: a comprehensive review of drug properties including clinical updates following recent FDA approval

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