Vitamin E pharmacokinetics in swine show low bioavailability of all‐rac α‐tocopheryl‐acetate

Vitamin E is important in animal production because of its beneficial effects on health and product quality. The form added to diets is usually all‐rac α‐Tocopheryl‐Acetate (α‐TAc). α‐TAc bioavailability is problematic because hydrolysis of the acetate ester maybe incomplete, while the 2 S ‐α‐T stereo‐isomers are poorly recognized by the α‐T‐transfer protein in the liver and thus poorly transferred into circulation. The objective of this work was to quantify α‐TAc bioavailability and pharmacokinetics. For this study, 17 piglets (BW 22±1 kg) were fitted with jugular catheters and adapted to twice daily feeding (350 g/meal) using a diet with 75 IU α‐TAc (commercial practice but 7xNRC, 2012). At 0 h, a meal containing 6% fat was supplied containing 75 IU D9 α‐TAc to 9 animals, while 8 animals received this diet without supplemental vit. E but instead an IV dose containing D6 RRR ‐α‐T at 1/8 th the oral α‐TAc dose, dissolved in 0.5 ml ethanol added to 4.5 ml Intralipid (Sigma). Plasma samples were obtained up to 75h for analysis of deuterated α‐T measured by LC/MS; results were standardized for dose and modeled as follows: Oral: Plateau*Ka*[exp(‐Ke*t)‐exp(‐ka*t)]/(Ka‐Ke) IV: Plateau*[Ka1*(exp(‐Ke1*t)‐exp(‐Ka1*t))/(Ka1‐Ke1)+Ka2*(exp(‐Ke2*t)‐exp(‐Ka2*t))/(Ka2‐Ke2)] Oral dosing resulted in a Ka (appearance rate) of 14.2±5.0 h and a Ke (elimination rate) of 4.9±1.7 h. Surprisingly, the IV dose disappeared rapidly from plasma, then reappeared; the initial clearance could not be adequately modeled as the first blood sample was only at 10 min. Hence, the Ka for the first peak was set to 4 sec (Ka1=10), in line with the time it took to administer the dose. The Ke1 for this first peak was only 1.7±0.3 min. The second peak had a Ka2 of 6.7±4.0 days and a Ke2 of 5.9±1.2 h, comparable to the Ke of the oral dose. Likely, the IV dose was quickly sequestered by the liver, then released slowly and cleared as usual. The plateau value for the IV‐administered vit. E was 15.9× higher (p<0.01) than for the oral dose when adjusted for administered quantity, suggesting that the bioavailability of orally administered α‐TAc was only 6.3% compared with intravenous RRR ‐α‐T. These low bio‐availabilities are likely because of the use of only 6% fat in the diet and the use of the acetate ester. In conclusion, IV dosed vit. E shows both a rapid and a very slow pool, while oral dosed vit. E shows a single moderately slow pool with an elimination rate of 4.9h, similar to the IV dose. The oral material, though, has a very poor bioavailability, estimated at 6.3%. Support or Funding Information Trouw Nutrition R&DModeled plasma concentrations for IV and orally dosed vitamin E