The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers

Clin Pharmacol Ther. 1996 Mar;59(3):297-303. doi: 10.1016/S0009-9236(96)80007-5.


We evaluated the effect of water-soluble vitamin E (d-alpha-tocopheryl polyethylene glycol 1000 succinate [TPGS]; Liqui-E) on the oral pharmacokinetics of the cyclosporine, a poorly available (approximately 30%) drug, in healthy volunteers. Ten healthy subjects were given two doses of oral cyclosporine (10mg/kg) separated by a 7-day washout period. Oral TPGS (2.6 IU/kg) was administered concomitantly with one of the cyclosporine doses in a randomized order. A significant increase was observed in area under the blood concentration-time curve (AUC;mean +/ SD) with concomitant TPGS administration (3908 +/- 2601 versus 6296 +/- 5102 ng x hr/ml). Significant decreases were observed in apparent oral clearance (0.24 +/- 0.14 versus 0.15 +/- 0.08 L/hr/kg) and apparent oral steady-state volume of distribution (1.57 +/- 0.95 versus 1.07 +/- 0.73 L/kg). No significant changes were observed in the ratios of metabolites to parent drug AUC values. The comparable relative decreases in apparent oral clearance (38%) and apparent oral steady-state volume of distribution (30%) with TPGS are most likely explained by enhanced absorption, decreased counter transport back into the intestine by P-glycoprotein, or some unknown mechanism by which cyclosporine is protected from metabolism in the gut, thereby increasing bioavailability.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Cross-Over Studies
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Reference Values
  • Solubility
  • Vitamin E / pharmacology*
  • Water


  • Immunosuppressive Agents
  • Water
  • Vitamin E
  • Cyclosporine