Comparison of α -tocopherol acetate preparations given as single intraperitoneal or subcutaneous doses for increasing plasma and liver α -tocopherol in sheep fed a low vitamin E diet

Abstract

This experiment examined the efficacy of a single dose of ß-tocopherol acetate (2000 IU) in either an aqueous or oily formulation, given as an intraperitoneal (i.p.) or subcutaneous (s.c.) injection or orally as an aqueous formulation, at raising a-tocopherol concentrations in blood plasma and liver of young sheep with low vitamin E. Maximum plasma concentrations (Cmax) were greatest in sheep supplemented by the s.c.-aqueous method or orally (4.83 and 3.49 mg/L respectively). These values were 3.0-5.7 times the C, values of the other treatment groups. Also, the time taken to reach Cmax (Tmax) was far shorter in these 2 treatments than in the other treatments (Tmax values were 0.70 and 0.65 days respectively). Tmax values were greatest for the oily formulation (42 and 73 days for the i.p. and S.C. injections, respectively). The area under the plasma a-tocopherol concentration-time curve (AUC(0-85d)), was greatest for the s.c.-aqueous group (median of 2066 mg.h/L). Six of the sheep in the i.p.-aqueous group had AUC(0-85d) values similar to the controls whereas the rest were similar to the s.c.-aqueous group. Plasma ß-tocopherol acetate was only consistently detected in sheep in the s.c.-aqueous group (Cmax of 25.25 ¦ 3.14 mg/L and Tmax of 0.24 ¦ 0.03 days). Pharmacokinetic modelling of the plasma data obtained from sheep in the s.c.-aqueous group was helpful in understanding the factors which controlled the appearance and disappearance rates of plasma ß-tocopherol in this group. In contrast to plasma data, liver concentrations of ß-tocopherol at days 24 and 57 were greatest in sheep supplemented by the i.p.-oily method. The s.c.-aqueous was the second most effective method at raising concentrations in the liver. The results suggest that supplementation by s.c. injection of an aqueous formulation may be an effective means of administering vitamin E to sheep.