Levels of total γ-aminobutyric acid (GABA), free GABA and homocarnosine in cerebrospinal fluid of epileptic patients before and during γ-vinyl-GABA (vigabatrin) treatment

Pitkänen, A.; Matilainen, Riitta; Ruutiainen, T; Riekkinen, P.

doi:10.1016/0022-510x(88)90207-9

Cited by 7 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 Oral administration also produces dosedependent lumbar cerebrospinal fluid (CSF) concentrations. [19][20][21][22] In a study of adult patients with drug-resistant complex partial epilepsy, single oral doses of 50 mg/kg produced vigabatrin CSF concentrations that were measurable within 6 hours of drug administration; only trace amounts were detectable at 24 hours. 23 Although the authors did not report individual vigabatrin CSF concentrations for each patient or time point, the average blood and CSF concentration profiles reveal that the postdose CSF concentrations at 6 and 24 hours were approximately 10-15% of concomitantly obtained blood concentrations.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…32 In human studies, vigabatrin administration produced dose-dependent increases in suboccipital and lumbar CSF GABA concentrations in patients with chronic epilepsy and those with newly diagnosed epilepsy. [19][20][21][22][23]33 One group of authors provided the most complete characterization of the area under the CSF GABA concentration-time curve. 23 After administration of single oral vigabatrin doses of 50 mg/kg to adult patients with drug-resistant complex partial epilepsy, increases in CSF GABA concentrations were noted within 6 hours, were significantly elevated by 24 hours, and remained elevated for at least 120 hours.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…[44][45][46][47] In addition, data exist to suggest inconsistent relationships between CSF vigabatrin concentrations, CSF GABA concentrations, and reductions in seizure frequency. 21,22,33 In a study of 75 patients with therapy-refractory complex partial epilepsy, CSF GABA and CSF vigabatrin concentrations were poorly correlated. 21 Although stratification of patients according to response revealed that responders had higher CSF GABA concentrations, vigabatrin CSF concentrations were not significantly different between these two groups.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…In a smaller study involving patients with a variety of seizure types, CSF GABA concentrations poorly correlated with CSF vigabatrin concentrations and seizure frequency reductions. 22 To account for these inconsistent relationships, some researchers have postulated that although the total CSF GABA pool may be increased with vigabatrin therapy, there may be specific areas of pathology in the epileptic brain that have limited capacity for a GABAergic response. 22…”

Section: Pharmacodynamicsmentioning

confidence: 99%

See 3 more Smart Citations

Vigabatrin for Infantile Spasms

2011

View full text Add to dashboard Cite

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.

show abstract

Section: Pharmacokineticsmentioning

confidence: 99%

Section: Pharmacodynamicsmentioning

confidence: 99%

Section: Pharmacodynamicsmentioning

confidence: 99%

Section: Pharmacodynamicsmentioning

confidence: 99%

See 2 more Smart Citations

Vigabatrin for Infantile Spasms

2011

View full text Add to dashboard Cite

show abstract

“…The inhibitory neurotransmitter GABA is degraded by GABA-T; blocking this enzyme increases the concentration of GABA, which is then thought to suppress abnormal electrical activity [ 8 ]. Vigabatrin given to epilepsy patients does increase GABA concentrations in CSF [ 9 – 11 ], and the CSF level of free GABA correlates with the CSF level of VGB [ 11 ]. However, there was no correlation between seizure frequency and CSF levels of GABA or VGB [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Monitoring vigabatrin in head injury patients by cerebral microdialysis: obtaining pharmacokinetic measurements in a neurocritical care setting

Shannon

Timofeev

Nortje

et al. 2014

Brit J Clinical Pharma

View full text Add to dashboard Cite

AimsThe aims were to determine blood–brain barrier penetration and brain extracellular pharmacokinetics for the anticonvulsant vigabatrin (VGB; γ-vinyl-γ-aminobutyric acid) in brain extracellular fluid and plasma from severe traumatic brain injury (TBI) patients, and to measure the response of γ-aminobutyric acid (GABA) concentration in brain extracellular fluid.MethodsSevere TBI patients (n = 10) received VGB (0.5 g enterally, every 12 h). Each patient had a cerebral microdialysis catheter; two patients had a second catheter in a different region of the brain. Plasma samples were collected 0.5 h before and 2, 4 and 11.5 h after the first VGB dose. Cerebral microdialysis commenced before the first VGB dose and continued through at least three doses of VGB. Controls were seven severe TBI patients with microdialysis, without VGB.ResultsAfter the first VGB dose, the maximum concentration of VGB (Cmax) was 31.7 (26.9–42.6) μmol l−1 (median and interquartile range for eight patients) in plasma and 2.41 (2.03–5.94) μmol l−1 in brain microdialysates (nine patients, 11 catheters), without significant plasma–brain correlation. After three doses, median Cmax in microdialysates increased to 5.22 (4.24–7.14) μmol l−1 (eight patients, 10 catheters). Microdialysate VGB concentrations were higher close to focal lesions than in distant sites. Microdialysate GABA concentrations increased modestly in some of the patients after VGB administration.ConclusionsVigabatrin, given enterally to severe TBI patients, crosses the blood–brain barrier into the brain extracellular fluid, where it accumulates with multiple dosing. Pharmacokinetics suggest delayed uptake from the blood.

show abstract