Disposition kinetics and dosage regimen of vitamin E administered intramuscularly to sheep.
Three experiments were conducted to estimate the effects of single intramuscular (IM) administrations of vitamin E on blood plasma and tissue concentrations of alpha-tocopherol in sheep. In Expt 1, plasma kinetics of alpha-tocopherol in sheep (n 30) were investigated following IM administration of three doses (ten sheep/dose) of DL-alpha-tocopheryl acetate, (20, 40 and 60 mg/kg live weight). Plasma profiles of alpha-tocopherol consisted of a lag phase followed by an apparent first-order absorption and elimination phase. The rate of absorption and elimination, as well as the lag phase, were independent of the dose, but the extent of absorption was directly proportional to dose. In Expt 2 (eighteen experimental and five control sheep), the animals were injected as in Expt 1 and were killed at 0, 80 and 176 h. Increases in alpha-tocopherol levels in organs were much higher than in plasma. Some tissues such as liver, spleen, lung and adrenal appeared to exhibit rapid absorption and elimination phases. The amount absorbed was proportional to the dose administered. Other organs such as heart, kidney and pancreas had a slow elimination rate. In Expt 3, D-alpha-tocopherol was injected IM into ten sheep at either 604 mg or 1208 mg. The mean hepatic alpha-tocopherol concentrations in both groups rose rapidly and after 4 weeks of dosing its concentrations were higher than the predosing levels. The increase in hepatic tocopherol concentrations were higher following 1208 mg dosing than 604 mg D-alpha-tocopherol. No simple relationship existed between plasma and hepatic alpha-tocopherol concentrations. This suggests a difference in body mechanisms controlling vitamin E in blood and liver.
Hidiroglou
M
M
Animal Research Centre, Agriculture Canada, Ottawa, Ontario.
Karpinski
K
K
D000818:Animals; D007273:Injections, Intramuscular; D008099:Liver / Q000378:metabolism; D008297:Male; D012756:Sheep / Q000378:metabolism*; D014018:Tissue Distribution; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D014810:Vitamin E; D024502:alpha-Tocopherol; D024505:Tocopherols