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This was achieved by evaluating plasma, liver and adrenal gland concentrations of <jats:sc>d<\/jats:sc>\u2010\u03b1\u2010tocopheryl succinate (TS) and <jats:sc>d<\/jats:sc>\u2010\u03b1\u2010tocopherol as well as oxidative status of plasma following oral dosing of TPGS\u2010containing vehicles, intraperitoneal (IP) dosing of TS or <jats:italic>ex vivo<\/jats:italic> treatment of blood with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Male and female rats were dosed orally with formulations containing 5% or 40% TPGS (70 or 550 mg kg<jats:sup>\u20131<\/jats:sup> day<jats:sup>\u20131<\/jats:sup> TS, respectively) for 1 week. A control group was dosed orally with polyethylene glycol\u2010400 (PEG\u2010400; no vitamin E) and positive control animals received a single 100 mg kg<jats:sup>\u20131<\/jats:sup> day<jats:sup>\u20131<\/jats:sup> IP injection of TS. Whole blood from untreated animals was treated <jats:italic>ex vivo<\/jats:italic> with 5 or 50 m<jats:sc>m<\/jats:sc> H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, with or without TS (0.5, 5, 50 or 500 \u03bc<jats:sc>m<\/jats:sc>) or ascorbate (1 m<jats:sc>m<\/jats:sc>), for 1 h. Oral TPGS treatments did not affect <jats:sc>d<\/jats:sc>\u2010\u03b1\u2010tocopherol concentrations in plasma or adrenal glands and caused only transient increases in liver. Concentrations of TS in plasma, liver and adrenal glands were undetectable in control animals, but increased in all other groups. Oral administration of TPGS did not reduce plasma lipid peroxidation <jats:italic>in vivo<\/jats:italic>. Substantially greater TS concentrations used <jats:italic>ex vivo<\/jats:italic> (100\u00d7 greater than <jats:italic>in vivo<\/jats:italic>) were also unable to reduce lipid peroxidation in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated whole blood. These results provide evidence that administration of oral TPGS vehicles is unlikely to impact nonclinical safety assessments of pharmaceuticals. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3072","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T01:17:36Z","timestamp":1414459056000},"page":"791-798","source":"Crossref","is-referenced-by-count":1,"title":["<scp>d<\/scp>\u2010\u03b1\u2010tocopheryl polyethylene glycol 1000 succinate\u2010containing vehicles provide no detectable chemoprotection from oxidative damage"],"prefix":"10.1002","volume":"35","author":[{"given":"Bethany R.","family":"Baumgart","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb Drug Safety Evaluation  Mt. Vernon IN 47620 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry R.","family":"Van Vleet","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Drug Safety Evaluation  Mt. 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