{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:24:41Z","timestamp":1785943481044,"version":"3.56.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T00:00:00Z","timestamp":1546819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY027476"],"award-info":[{"award-number":["R01 EY027476"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res & Perspec"],"published-print":{"date-parts":[[2019,2]]},"abstract":"Abstract<\/jats:title>Vigabatrin (VGB<\/jats:styled-content>; (S)\u2010(+)\/(R)\u2010(\u2010)<\/jats:italic> 4\u2010aminohex\u20105\u2010enoic acid), an antiepileptic irreversibly inactivating GABA<\/jats:styled-content> transaminase (GABA<\/jats:styled-content>\u2010T), manifests use\u2010limiting ocular toxicity. Hypothesizing that the active S<\/jats:italic> enantiomer of VGB<\/jats:styled-content> would preferentially accumulate in eye and visual cortex (VC<\/jats:styled-content>) as one potential mechanism for ocular toxicity, we infused racemic VGB<\/jats:styled-content> into mice via subcutaneous minipump at 35, 70, and 140\u00a0mg\/kg\/d (n\u00a0=\u00a06\u20108 animals\/dose) for 12\u00a0days. VGB<\/jats:styled-content> enantiomers, total GABA<\/jats:styled-content> and \u03b2\u2010alanine (BALA<\/jats:styled-content>), 4\u2010guanidinobutyrate (4\u2010GBA<\/jats:styled-content>), and creatine were quantified by mass spectrometry in eye, brain, liver, prefrontal cortex (PFC<\/jats:styled-content>), and VC<\/jats:styled-content>. Plasma VGB<\/jats:styled-content> concentrations increased linearly by dose (3\u00a0\u00b1\u00a00.76 (35\u00a0mg\/kg\/d); 15.1\u00a0\u00b1\u00a01.4 (70\u00a0mg\/kg\/d); 34.6\u00a0\u00b1\u00a03.2\u00a0\u03bcmol\/L (140\u00a0mg\/kg\/d); mean\u00a0\u00b1\u00a0SEM) with an S<\/jats:italic>\/R<\/jats:italic> ratio of 0.74\u00a0\u00b1\u00a00.02 (n\u00a0=\u00a014). Steady state S<\/jats:italic>\/R<\/jats:italic> ratios (35, 70\u00a0mg\/kg\/d doses) were highest in eye (5.5\u00a0\u00b1\u00a00.2; P<\/jats:italic>\u00a0<\u00a00.0001), followed by VC<\/jats:styled-content> (3.9\u00a0\u00b1\u00a00.4), PFC<\/jats:styled-content> (3.6\u00a0\u00b1\u00a00.3), liver (2.9\u00a0\u00b1\u00a00.1), and brain (1.5\u00a0\u00b1\u00a00.1; n\u00a0=\u00a013\u201014 each). Total VGB<\/jats:styled-content> content of eye exceeded that of brain, PFC<\/jats:styled-content> and VC<\/jats:styled-content> at all doses. High\u2010dose VGB<\/jats:styled-content> diminished endogenous metabolite production, especially in PFC<\/jats:styled-content> and VC<\/jats:styled-content>. GABA<\/jats:styled-content> significantly increased in all tissues (all doses) except brain; BALA<\/jats:styled-content> increases were confined to liver and VC<\/jats:styled-content>; and 4\u2010GBA<\/jats:styled-content> was prominently increased in brain, PFC<\/jats:styled-content> and VC<\/jats:styled-content> (and eye at high dose). Linear correlations between enantiomers and GABA<\/jats:styled-content> were observed in all tissues, but only in PFC<\/jats:styled-content>\/VC<\/jats:styled-content> for BALA<\/jats:styled-content>, 4\u2010GBA<\/jats:styled-content>, and creatine. Preferential accumulation of the VGB <\/jats:styled-content>S<\/jats:italic> isomer in eye and VC<\/jats:styled-content> may provide new insight into VGB<\/jats:styled-content> ocular toxicity.<\/jats:p>","DOI":"10.1002\/prp2.456","type":"journal-article","created":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T16:54:03Z","timestamp":1546966443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use\u2010limiting visual field defects"],"prefix":"10.1002","volume":"7","author":[{"given":"Dana C.","family":"Walters","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin E. 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