他汀的联合降脂治疗课件.ppt

Combination Lipid-Altering Drug Therapy with Statins Combination Lipid-Altering Drug Therapy with Statins Need for combination lipid-altering drug therapy Ezetimibe and statins Bile acid sequestrants and statins PPAR agonists and statins Fish oils and statins Niacin and statins NCEP ATP III LDL-C Treatment Goals Inadequate Achievement of NCEP ATP III Treatment Goals, Especially among Patients at Highest Risk Majority of LDL-C Lowering Occurs at the Lowest Statin Dose Three Sources of Cholesterol Intestinal Cholesterol Absorption Ezetimibe: Mechanism of Action Ezetimibe selectively inhibits intestinal cholesterol absorption ? intestinal delivery of cholesterol to the liver ? expression of hepatic LDL receptors ? cholesterol content of atherogenic particles Ezetimibe and its active glucuronide metabolite circulate enterohepatically Delivers agent back to the site of action Limits systemic exposure Ezetimibe: EfficacyDose–Response Study Ezetimibe: EfficacyAdd On Study Ezetimibe: Efficacy—Add On Study Ezetimibe: Metabolism Ezetimibe undergoes glucuronidation in the intestinal wall and is then metabolized to its active glucuronide metabolite in the liver and delivered back to the intestine for enterohepatic recirculation The enterohepatic recirculation helps account for ezetimibe’s 22-hour half-life Ezetimibe is not an inducer or inhibitor of cytochrome P450 enzymes, reducing the risk for potential drug interactions with many common drugs enzymatically affected by cytochrome P450 enzymes Ezetimibe: MetabolismLow Systemic Exposure to Ezetimibe Ezetimibe: Drug Interactions Statins: No significant pharmacokinetic interactions Cholestyramine: Decreased the mean AUC of total ezetimibe concentration by 55%. Ezetimibe should be administered ?2 hours before or ?4 hours after a resin Fibrates: Not currently recommended in combination with ezetimibe, as safety and efficacy has not yet been established by clinical trials. Cyclosporin: May substantially increase ezetimibe