Ezetimibe - Biochemistry - Lecture Slides, Slides of Biochemistry

Download Ezetimibe - Biochemistry - Lecture Slides and more Slides Biochemistry in PDF only on Docsity! Pathway of Exogenous Cholesterol Metabolism INTESTINAL LUMEN LYMPH BLOOD Chylomicrons BILIARY TRACT Remnants DIET Micelles Free cholesterol C h o le s te ro l Bile acids Unstirred water layer Synthesis FC biosynthesis ACAT Cholesteryl Ester (CE) FC ENTEROCYTE B ru s h B o rd e r Plaque formation CE CE Docsity.com Complementary Mechanisms of Action Lead to Broader Lipid Control DIETARY CHOLESTEROL BILIARY SECRETION INTESTINE Excretion VLDL LDL Absorption synthesis IDL Statins Cholesterol Absorption Inhibition Docsity.com Ezetimibe Phase III Monotherapy: Pooled Safety Results Placebo Ezetimibe (n=431) (n=1288) Adverse events 285 (66) 802 (62) Gastrointestinal 93 (22) 230 (18) DC 2° AE 11 (2.6) 51 (4) Liver function tests (3 x ULN) ALT 2 (<1) 7 (<1) AST 3 (<1) 6 (<1) GGT 10 (2) 20 (2) Total bilirubin 0 0 ALP 0 0 Creatine kinase (CK) elevations 5-10 x ULN 0 8 (<1) 10 x ULN 1 (<1) 3 (<1) No. of Patients/Total (%) Docsity.com -60 -50 -40 -30 -20 -10 0 10 20 m e a n % c h a n g e f ro m b a s e li n e + Pbo -24,7 4,0 -11,2 -24,3 6,7 -7,6 -36,1 6,9 -16,6 -42,4 4,3 -21,5 + EZE -39 8,6 -21,7 -37,7 8,1 -17,6 -49,9 9,3 -24,1 -54,5 7,3 -29,5 LDL HDL TG LDL HDL TG LDL HDL TG LDL HDL TG Results: Added Efficacy Across the Lipid Profile Regardless of Statin Used Lovastatin Pravastatin Simvastatin Atorvastatin * * * * * * * * ‡ * * * Docsity.com • Ezetimibe co-administered with low dose statins, offers broader lipid control than that achieved by increasing the dose of the statin alone Ezetimibe Co-administered with Statins HDL–C LDL–C TG Additional -14 to 18 % Additional -10% Additional 5% 40% 6% 20% TG Docsity.com