The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers.
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.
Chang
T
T
Department of Pharmacy, Division of Clinical Pharmacy, University of California, San Francisco, 94143-0446, USA.
Benet
L Z
LZ
Hebert
M F
MF
D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D012016:Reference Values; D012995:Solubility; D014810:Vitamin E / Q000494:pharmacology*; D014867:Water
D007166:Immunosuppressive Agents; D014867:Water; D014810:Vitamin E; D016572:Cyclosporine