Vitamin E delta-tocotrienol levels in tumor and pancreatic tissue of mice after oral administration

Pharmacology. 2009;83(3):157-63. doi: 10.1159/000190792. Epub 2009 Jan 13.


Tocotrienols are natural vitamin E compounds that are known to have a neuroprotective effect at nanomolar concentration and anti-carcinogenic effect at micromolar concentration. In this report, we investigated the pharmacokinetics, tumor and pancreatic tissue levels, and toxicity of delta-tocotrienol in mice because of its anti-tumor activity against pancreatic cancer. Following a single oral administration of delta-tocotrienol at 100 mg/kg, the peak plasma concentration (C(max)) was 57 +/- 5 micromol/l, the time required to reach peak plasma concentration (T(max)) was 2 h and plasma half-life (t(1/2)) was 3.5 h. The delta-tocotrienol was cleared from plasma and liver within 24 h, but delayed from the pancreas. When mice were fed delta-tocotrienol for 6 weeks, the concentration in tumor tissue was 41 +/- 3.5 nmol/g. This concentration was observed with the oral dose (100 mg/kg) of delta-tocotrienol which inhibited tumor growth by 80% in our previous studies. Interestingly, delta-tocotrienol was 10-fold more concentrated in the pancreas than in the tumor. We observed no toxicity due to delta-tocotrienol as mice gained normal weight with no histopathological changes in tissues. Our data suggest that bioactive levels of delta-tocotrienol can be achieved in the pancreas following oral administration and supports its clinical investigation in pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Line, Tumor
  • Female
  • Half-Life
  • Liver / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Pancreas / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / prevention & control
  • Tissue Distribution
  • Transplantation, Heterologous
  • Vitamin E / administration & dosage
  • Vitamin E / analogs & derivatives*
  • Vitamin E / blood
  • Vitamin E / pharmacokinetics
  • Vitamin E / toxicity


  • Vitamin E
  • tocotrienol, delta