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GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs

Guerrouahen, Bella et al.

BMC cancer. Volume 16:Issue 1 (2016); pp 1-16 -- BioMed Central

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  • Title:
    GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs
  • Author: Guerrouahen, Bella;
    Hahn, Tobias;
    Alderman, Zefora;
    Curti, Brendan;
    Urba, Walter;
    Akporiaye, Emmanuel
  • Found In: BMC cancer. Volume 16:Issue 1 (2016); pp 1-16
  • Journal Title: BMC cancer
  • Subjects: Cancer--Periodicals; Cancer therapy--Vitamin analog--α-TEA lysine salt--Toxicokinetic--Pharmacokinetics--Non-rodent; Dewey: 616.994005
  • Rights: legaldeposit
  • Publication Details: BioMed Central
  • Abstract: AbstractBackgroundAlpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period.MethodsMale and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied.ResultsOur findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment.ConclusionWe demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer.
  • Identifier: System Number: LDEAvdc_100080997662.0x000001; Journal ISSN: 1471-2407; 10.1186/s12885-016-2220-6
  • Publication Date: 2016
  • Physical Description: Electronic
  • Shelfmark(s): ELD Digital store

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