Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures

Vauzelle-Kervroëdan, F; E, Rey; Pons, Gérard; d'Athis, P; Chiron, Catherine; Dulac, Olivier; Dumas, C.; Olivé, G

doi:10.1046/j.1365-2125.1996.00495.x

Cited by 22 publications

(8 citation statements)

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“…12,[14][15][16] This time is longer in elderly subjects with compromised renal function 12 and pediatric patients with refractory epilepsy (Table 1). 17,18 Administration of a 1-g dose with a standard breakfast has been shown to reduce the vigabatrin C max (mean ± SD 30.5 ± 4.3 µg/ml fasting vs 25.8 ± 7.2 µg/ml with food, p=0.04), but the T max and the AUC are not altered. 16 The mean ± SD bioavailability after administration with a standard breakfast relative to fasting administration is 92.0 ± 11.8%.…”

Section: Pharmacokineticsmentioning

confidence: 98%

“…In another study of neonates (mean ± SD age 21.3 ± 4.2 days), the Renantiomer C max and AUC were also higher than those of the S-enantiomer, producing mean ratios of R-enantiomer:S-enantiomer C max and AUC of 2.4 and 1.6, respectively ( Table 1). 17 Preliminary findings from a study in children, which was not subsequently published, revealed that the Renantiomer CSF concentrations were greater than those of the S-enantiomer. 28 Similar patterns in the enantiomers have been observed in healthy adult volunteers after administration of a single 1500-mg (mean ± SD 19.5 ± 2.9 mg/kg) oral dose (Table 1).…”

Section: Pharmacokineticsmentioning

confidence: 99%

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Vigabatrin for Infantile Spasms

2011

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Infantile spasms describe a pediatric epilepsy syndrome characterized by frequent clusters of brief symmetric muscle contractions; the condition is often associated with developmental delay. When infantile spasms are accompanied by hypsarrhythmia on electroencephalogram, the condition is labeled West syndrome. The mainstay of treatment for infantile spasms is adrenocorticotropic hormone; however, vigabatrin, a vinyl derivative of γ-aminobutyric acid, has been used for the treatment of infantile spasms in Europe since 1989. In 2009, vigabatrin was approved by the United States Food and Drug Adminstration (FDA) for use as monotherapy in the treatment of infantile spasms in patients aged 1 month-2 years when the benefits of treatment outweigh the risks. Results from numerous trials examining the role of vigabatrin in infantile spasms have been published; many of these trials were small, open-label, or noncontrolled. Although clinical trials have provided some insight into the utility of vigabatrin for the treatment of infantile spasms, these studies have notable limitations. In addition, vigabatrin is associated with a black-box warning that describes the potential for permanent bilateral concentric visual field defects. Currently, vigabatrin is available through a manufacturer-sponsored program in accordance with its FDA-approved Risk Evaluation and Mitigation Strategy. Although several guidelines recommend vigabatrin as a first-line therapy for infantile spasms, specifically infantile spasms related to tuberous sclerosis, it is still unclear whether vigabatrin should supersede hormone therapy as first-line therapy. Further research comparing the two therapies is needed.

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Section: Pharmacokineticsmentioning

confidence: 98%

Section: Pharmacokineticsmentioning

confidence: 99%

Vigabatrin for Infantile Spasms

2011

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“…This study proposed that a similar weight‐normalized dose of vigabatrin racemate could theoretically be given from to children aged 1 month‐15 years. A lower (S)‐vigabatrin exposure (ie, approximately 50% of [R]‐vigabatrin exposure) was also observed in neonates (aged 21.3 ± 4.2 days) with uncontrolled seizures . However, the AUC of (S)‐vigabatrin was higher than that observed in infants (+56%) and children (+21%), suggesting a possible age‐related change of (S)‐vigabatrin PK parameters during childhood.…”

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confidence: 84%

Proposition of a Minimal Effective Dose of Vigabatrin for the Treatment of Infantile Spasms Using Pediatric and Adult Pharmacokinetic Data

Ounissi

Rodrigues

Bienaymé

et al. 2018

The Journal of Clinical Pharma

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Vigabatrin is an antiepileptic drug indicated as monotherapy in infantile spasms. However, the pharmacokinetic profile of this compound in infants and young children is still poorly understood, as is the minimal effective dose, critical information given the risk of exposure-related retinal toxicity with vigabatrin. A reasonable approach to determining this minimal dose would be to identify the lowest dose providing a low risk of exposure overlap with the 36-mg/kg dose, which is the highest dose associated with an increased risk for treatment failure, based on randomized dose-ranging data. A population pharmacokinetic model was consequently developed from 28 children (aged 0.4-5.7 years) for the active S(+)-enantiomer, using Monolix software. In parallel, a population model was developed from published adult data and scaled to children using theoretical allometry and maturation of the renal function. A one-compartment model with zero-order absorption and first-order elimination described the pediatric data. Mean population estimates (percentage interindividual variability) for the apparent clearance, apparent distribution volume, and absorption duration were 2.36 L/h (24.5%), 17 L (38%), and 0.682 hours, respectively. Apparent clearance and apparent distribution volume were related to body weight by empirical allometric equations. Monte Carlo simulations evidenced that a daily dose of 80 mg/kg should minimize exposure overlap with the 36-mg/kg dose. Similar results were obtained for the adult model scaled to children. Consequently, a minimal effective dose of 80 mg/kg/day could be considered for patients with infantile spasms.

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“…106 A single study reported the pharmacokinetics of vigabatrin in neonates with uncontrolled seizures. 107 Peripheral vision loss is an adverse effect that has been reported in around 15% in children, 108 and because the risk of vision loss cannot be tested in newborns, vigabatrin should not be used as an option to treat neonatal convulsions. 57 Lamotrigine is well tolerated in children, but evidence of its clinical application and efficacy in neonates is very limited.…”

Section: Treatment Optionsmentioning

confidence: 99%

Management of refractory neonatal seizures

Neubauer¹,

Soltirovska-Šalamon²,

Osredkar³

et al. 2014

RRN

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The risk of seizures is highest during the neonatal period. Currently used therapies have limited efficacy and the treatment of neonatal seizures has not significantly changed in recent decades. Controversies still exist as to whether neonatal seizures can cause damage to the developing brain per se, or if the associated neurodevelopmental problems are caused by the underlying condition(s). However, during recent years, there has been substantial progress in the diagnostic possibilities for uncovering the etiologic cause of seizures. This article addresses the most common and important (treatable) etiologic causes of neonatal seizures, and discusses some of the diagnostic tools available. Current therapeutic approaches and their efficacy are discussed, with the aim to present the current knowledge on the topic.

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Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures

Cited by 22 publications

References 0 publications

Vigabatrin for Infantile Spasms

Vigabatrin for Infantile Spasms

Proposition of a Minimal Effective Dose of Vigabatrin for the Treatment of Infantile Spasms Using Pediatric and Adult Pharmacokinetic Data

Management of refractory neonatal seizures

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