The aim of this work was to compare the intestinal absorption kinetics and bioavailability of γ-tocotrienol (γ-T3) and α-tocopherol (α-Tph) administered separately as oil solutions to rats invivo. Also, to explain the significant difference in both compounds oral bioavailability bycomparing their: 1) release profiles using the dynamic in-vitro lipolysis model, 2) intestinalpermeability, and 3) carrier-mediated uptake by Niemann-Pick C1-like 1 (NPC1L1) transporterwere examined. Absolute bioavailability studies were conducted after oral administration of γ-T3 or α-Tph prepared in corn oil to rats. In-situ rat intestinal perfusion with ezetimibe (NPC1L1 inhibitor) was performed to compare intestinal permeability. In-vitro interaction kinetics with NPC1L1 was examined in NPC1L1 transfected cells. While the in-vitro release studies demonstrated significantly higher release rate of γ-T3 in the aqueous phase, the oral bioavailability of α-Tph (36%) was significantly higher than γ-T3 (9%). Consequent in-situ studies revealed significantly higher intestinal permeability for α-Tph compared to γ-T3 in rats. Moreover, NPC1L1 kinetic studies demonstrated higher Vmax and Km values for α-Tph compared to γ-T3. Collectively, these results indicate that intestinal permeability is the main contributing factor for higher bioavailability of α-Tph. Also, these results emphasize the potentially important role of intestinal permeability in the bioavailability of γ-T3 suggesting that enhancing its permeability would increase its oral bioavailability.
