Ezetimibe-d4 is intended for use as an internal standard for the quantification of ezetimibe by GC- or LC-MS. Ezetimibe inhibits intestinal cholesterol absorption by preventing cholesterol uptake by the Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter located in the apical membrane of enterocytes.1,2 Upon oral administration ezetimibe undergoes rapid glucuronidation in the intestine where its glucuronide binds NPC1L1.1,2 Ezetimibe exhibits ED50 values of 0.0005-0.05 mg/kg in various animal models, selectively blocking cholesterol absorption without inhibiting pancreatic lipolytic enzyme activities in the intestinal lumen, affecting bile acid micelle solubilization of cholesterol, or interfering with the absorption of triglycerides, fatty acids, or bile acids.1,3
1.Wang, D.Q.Regulation of intestinal cholesterol absorptionAnnu. Rev. Physiol.69221-248(2007) 2.Garcia-Calvo, M., Lisnock, J., Bull, H.G., et al.The target of ezetimibe is Niemann-Pick C1-like 1 (NPC1L1)Proc. Natl. Acad. Sci. USA102(23)8132-8137(2005) 3.Sudhop, T., and von Bergmann, K.Cholesterol absorption inhibitors for the treatment of hypercholesterolaemiaDrugs62(16)2333-2347(2002)