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  • 标题:Tolerability and pharmacokinetics of oxaloacetate 100mg capsules in Alzheimer's subjects
  • 作者:Russell H. Swerdlow ; Rebecca Bothwell ; Lewis Hutfles
  • 期刊名称:BBA Clinical
  • 印刷版ISSN:2214-6474
  • 出版年度:2016
  • 卷号:5
  • 页码:120-123
  • DOI:10.1016/j.bbacli.2016.03.005
  • 出版社:Elsevier B.V.
  • 摘要:

    Bioenergetics and bioenergetic-related functions are altered in Alzheimer's disease (AD) subjects. These alterations represent therapeutic targets and provide an underlying rationale for modifying brain bioenergetics in AD-affected persons. Preclinical studies in cultured cells and mice found that administering oxaloacetate (OAA), a Krebs cycle and gluconeogenesis intermediate, enhanced bioenergetic fluxes and upregulated some brain bioenergetic infrastructure-related parameters. We therefore conducted a study to provide initial data on the tolerability and pharmacokinetics of OAA in AD subjects. Six AD subjects received OAA 100 mg capsules twice a day for one month. The intervention was well-tolerated. Blood level measurements following ingestion of a 100 mg OAA capsule showed modest increases in OAA concentrations, but pharmacokinetic analyses were complicated by relatively high amounts of endogenous OAA. We conclude that OAA 100 mg capsules twice per day for one month are safe in AD subjects but do not result in a consistent and clear increase in the OAA blood level, thus necessitating future clinical studies to evaluate higher doses.

  • 关键词:Alzheimer's disease ; Clinical trial ; Mitochondria ; Oxaloacetate ; Pharmacokinetics
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