| Abstract: | Tocopherol is used not only as an ethical drug but also as a supplement. In 2008, it was reported that α‐tocopherol is partly transported via an intestinal cholesterol transporter, Niemann‐Pick C1‐Like 1 (NPC1L1). Ezetimibe, a selective inhibitor of NPC1L1, is administered for a long time to inhibit cholesterol absorption and there is a possibility that the absorption of α‐tocopherol is also inhibited by ezetimibe. This study investigated the influence of ezetimibe on the absorption of α‐tocopherol with single administration and long‐term administration. An approach to avoid its undesirable consequence was also examined. α‐Tocopherol (10 mg/kg) and ezetimibe (0.1 mg/kg) were administered to rats, and the plasma concentration profiles of α‐tocopherol and tissue concentrations were investigated. The plasma concentration of α‐tocopherol was decreased by the combination use of ezetimibe in the case of concurrent single administration. On the other hand, inhibition of the absorption of α‐tocopherol was prevented by an administration interval of 4 h. In a group of rats administered for 2 months with a 4 h interval, not only the plasma concentration but also the liver concentration was increased compared with those in a group with concurrent combination intake of α‐tocopherol and ezetimibe. The absorption of α‐tocopherol was inhibited by ezetimibe. The inhibitory effect of ezetimibe can be prevented by an administration interval of 4 h, although ezetimibe is a medicine of enterohepatic circulation. Attention should be paid to the use of ezetimibe and components of NPC1L1 substrates such as α‐tocopherol. Copyright © 2016 John Wiley & Sons, Ltd. |
