Fig. 5.

Proposed mechanism of the drug interaction between ezetimibe and warfarin.

Vitamin K (VK) is absorbed by NPC1L1 in the intestine and then circulates through the vitamin K cycle in the liver. In this cycle, vitamin K activates clotting factors and regulates blood coagulation. When warfarin, an anticoagulant drug that inhibits the vitamin K cycle, and ezetimibe, an NPC1L1 inhibitor clinically used for dyslipidemia, are administered together, the anticoagulant effect of warfarin is apparently enhanced by the ezetimibe-related reduction in vitamin K absorption.