Concurrent administration of water-soluble vitamin E can increase the oral bioavailability of cyclosporine a in healthy dogs.
Randomized crossover studies were performed to determine the effect of coadministration of d-alpha-tocopheryl polyethylene glycol 1,000 succinate (vitamin E TPGS) on the oral bioavailability of cyclosporine A (CsA) formulated as either Sandimmune (Novartis Pharmaceuticals) or Neoral (Novartis Pharmaceuticals). Healthy dogs were given a single oral dose of each cyclosporine formulation with and without vitamin E TPGS. Blood samples were collected from each dog before and at various intervals for 24 hours after drug administration. Whole-blood CsA concentrations were determined by high-pressure liquid chromatography. Noncompartmental pharmacokinetic analysis showed that coadministration of vitamin E TPGS increased the oral bioavailability of Sandimmune. The bioavailability of Neoral was greater than that of cyclosporine. Concurrent administration of vitamin E TPGS had no consistent effect on the bioavailability of Neoral.
Fischer
Julie R
JR
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
Harkin
Kenneth R
KR
Freeman
Lisa C
LC
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012995:Solubility; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; D014810:Vitamin E; D016572:Cyclosporine