2019
DOI: 10.1002/prp2.456
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Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use‐limiting visual field defects

Abstract: Vigabatrin (VGB; (S)‐(+)/(R)‐(‐) 4‐aminohex‐5‐enoic acid), an antiepileptic irreversibly inactivating GABA transaminase (GABA‐T), manifests use‐limiting ocular toxicity. Hypothesizing that the active S enantiomer of VGB would preferentially accumulate in eye and visual cortex (VC) as one potential mechanism for ocular toxicity, we infused racemic VGB into mice via subcutaneous minipump at 35, 70, and 140 mg/kg/d (n = 6‐8 animals/dose) for 12 days. VGB enantiomers, total GABA and β‐alanine (BALA), 4‐guanidinobu… Show more

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Cited by 12 publications
(18 citation statements)
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“…Preparation and purification of VGB, as well as subcutaneous infusion of VGB to mice, has been recently described (Walters et al 2019). In brief, C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME) were bred in-house to obtain required cohort size (n=6-8 per dose group, male only), and were 8-10 weeks of age and 20.8-26.1 g in weight.…”
Section: Methodsmentioning
confidence: 99%
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“…Preparation and purification of VGB, as well as subcutaneous infusion of VGB to mice, has been recently described (Walters et al 2019). In brief, C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME) were bred in-house to obtain required cohort size (n=6-8 per dose group, male only), and were 8-10 weeks of age and 20.8-26.1 g in weight.…”
Section: Methodsmentioning
confidence: 99%
“…Animals were randomly assigned to vehicle or drug cohorts. Loading of pumps, surgical implantation, and duration of use (12 days) has been described (Walters et al 2019). Tissues isolated for analysis included intact eye, liver, prefrontal cortex (PFC, including both gray and white matter), visual cortex (VC), the remainder of the intact brain, and plasma.…”
Section: Methodsmentioning
confidence: 99%
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“…This VGB dose of 140 mg/kg/d was based on human clinical doses. 2 VGB was synthesized as described in Walters et al, 2019 17 for the first cohort of 12 C57BL/6J mice (n = 6 per treatment group) and purchased from Sigma-Aldrich (St. Louis, MO) for the second and third cohorts of mice (n = 12 per treatment group).…”
Section: Vgb Treatmentmentioning
confidence: 99%
“…The tissues were stored at -80°C and shipped on dry ice for extraction and quantification of VGB and GABA concentrations in tissue samples, performed as described by Walters et al. 17…”
Section: Mass Spectrometrymentioning
confidence: 99%