Effect of alpha tocopherol (vitamin E) deficiency on intestinal transport of passively absorbed drugs.
Alpha tocopherol (vitamin E) deficiency has been shown to cause changes in membrane structure. The present study relates alpha tocopherol deficiency with increased rates of transport and absorption of passively absorbed drugs. The pharmacokinetics of barbital in alpha tocopherol-deficient and control rats was studied. The barbital absorption rate constant in deficient animals increased compared to control values. This findings indicates that alpha tocopherol deficiency affects the intestinal membrane structure. This finding was confirmed by studying the intestinal transport of phenolsulfonphthalein, barbital, and salicylate using the everted gut technique. Phenolsulfonphthalein was transported more rapidly through the alpha tocopherol-deficient gut, but this difference was not significant after 30 min, probably due to membrane decomposition. Barbital, which is more lipid soluble and less dependent on changes in pore volume and size, was transported more rapidly through the deficient gut during the entire experiment. The transport rate of salicylate was not altered by the deficiency state. This result was expected since the drug is normally rapidly transported; therefore, comparatively small changes in permeability such as those induced by alpha tocopherol deficiency would be masked. After the oral administration of phenolsulfonphthalein to intact animals, a significantly higher amount of drug was recovered in the urine of the deficient group.
D000818:Animals; D001462:Barbital / Q000378:metabolism / Q000652:urine; D001692:Biological Transport; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000378:metabolism; D051381:Rats; D012459:Salicylates / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D012459:Salicylates; D001462:Barbital; D010637:Phenolsulfonphthalein