Ezetimibe in hypercholesterolaemia.

Abstract

Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors, compounds that effectively block intestinal absorption of dietary and biliary cholesterol, without affecting absorption of fat soluble vitamins or triglycerides. Ezetimibe underwent glucuronidation to a single metabolite and localised at the intestinal wall, where it prevented luminal cholesterol absorption. Pre-clinical studies demonstrated the lipid-lowering and antiatherosclerotic properties of ezetimibe. The efficacy and safety of ezetimibe monotherapy have been determined in phase II/III studies: in phase II studies, the optimal efficacy was reached with ezetimibe 10 mg per day and the pooled efficacy data have shown that ezetimibe 10 mg has a positive effect on the lipoprotein profile with a significant reduction in LDL-cholesterol of 18.5%, an increase in HDL-cholesterol of 3.5% and a trend towards lowering in triglyceride concentrations (-4.9%). The monotherapy phase III studies have confirmed the efficacy with a decrease in LDL-C of 17.4% and have demonstrated an excellent safety and tolerability profile. The potential for a pharmacokinetic and/or pharmacodynamic interaction between ezetimibe and various statins and the efficacy and safety or the co-administration of ezetimibe and statins have been evaluated in different phase I/II studies: ezetimibe had no significant effect on the pharmacokinetics of simvastatin or atorvastatin. Ezetimibe 10 mg co-administrated with the starting dose of any statin induced a mean 18% additive LDL-C lowering effect. This additive 18% reduction in LDL-C is achieved in one step compared with the three steps necessary with statin monotherapy.