Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease

Farnier, Michel; Volpe, Massimo; Massaad, Rachid; Davies, Michael J.; Allen, Christopher

doi:10.1016/j.ijcard.2005.01.022

Cited by 47 publications

(20 citation statements)

References 30 publications

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“…The effects of combining ezetimibe with fenofibrate on atherogenic lipid profile have also been evaluated 42,43) . In a multicenter, double-blind, randomized trial, 625 patients with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL), were randomized in a 3:3:3:1 ratio to one of 4 treatments for 12 weeks: ezetimibe 10 mg, fenofibrate 160 mg, fenofibrate 160 mg plus ezetimibe 10 mg, and placebo 42) .…”

Section: Ezetimibe and Ezetimibe/simvastatin In Combination With Fenomentioning

confidence: 99%

“…In a multicenter, double-blind, randomized trial, 625 patients with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL), were randomized in a 3:3:3:1 ratio to one of 4 treatments for 12 weeks: ezetimibe 10 mg, fenofibrate 160 mg, fenofibrate 160 mg plus ezetimibe 10 mg, and placebo 42) . After completing the 12-week study, 576 patients continued into a double-blind, 48-week extension phase comparing fenofibrate (n 236) to fenofibrate plus ezetimibe (n 340) 43) Patients in the fenofibrate plus ezetimibe and fenofibrate groups continued on their respective previous treatment, and patients in the ezetimibe and placebo groups were switched to fenofibrate plus ezetimibe and fenofibrate, respectively.…”

Section: Ezetimibe and Ezetimibe/simvastatin In Combination With Fenomentioning

confidence: 99%

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Zetia: Inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to Reduce Intestinal Cholesterol Absorption and Treat Hyperlipidemia

Davis¹,

Veltri²

2007

J Atheroscler Thromb

145

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Zetia (ezetimibe) is a selective cholesterol absorption inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids. Ezetimibe reduces the small intestinal enterocyte uptake and absorption of cholesterol by binding to Niemann-Pick C1 Like 1 (NPC1L1), which keeps cholesterol in the intestinal lumen for excretion. Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it binds with higher affinity for NPC1L1 than ezetimibe to prevent cholesterol absorption. Enterohepatic recirculation of ezetimibe and/or its glucuronide ensures repeated delivery to the intestinal site of action and limited peripheral exposure. Ezetimibe has no effect on the activity of major drug metabolizing enzymes (CYP450), which reduces any potential drug-drug interactions with other medications. Ezetimibe (10 mg/day) was found to inhibit cholesterol absorption by an average of 54% in hypercholesterolemic individuals and by 58% in vegetarians. Ezetimibe alone reduced plasma total and LDL-Cholesterol (18%) levels in patients with primary hypercholesterolemia. When ezetimibe was added to on-going statin treatment, an additional 25% reduction in LDL-C was found in patients with primary hypercholesterolemia and an additional 21% reduction in LDL-C in homozygous familial hypercholesterolemia. Ezetimibe in combination with statins produces additional reductions in plasma cholesterol levels and allows for more patients to achieve their LDL-C goals. . Zetia was identified through the characterization of the active biliary metabolites of its predecessor, SCH 48461, and extensive structure-activity relationship information obtained from a seven day cholesterol-fed hamster model 2) . Ezetimibe dose-dependently inhibited diet-induced hypercholesterolemia in hamsters with an ED50 of 0.04 mg/kg. In an acute model of intestinal absorption using radiolabeled cholesterol in rats, ezetimibe inhibited the appearance of radiolabeled cholesterol in plasma with an ED50 of 0.0015 mg/kg ninety minutes after dosing, indicating that the onset of activity was rapid 3) . Ezetimibe has proven to be most potent pre-clinically in cholesterol-fed rhesus monkeys with an ED50 0.0005 mg/kg/day. A single dose of the ezetimibe analog, SCH 48461, administered to cynomolgus monkeys fed a single cholesterol-containing meal caused a significant reduction of cholesterol in chylomicrons and chylomicron remnants during the postprandial phase without affecting triglyceride content 4) . Ezetimibe selectively inhibits the transport of cholesterol across the intestinal wall. Ezetimibe does not affect intestinal cholesteryl ester hydrolysis and the absorption of fatty acids thus generated. The free cholesterol from this hydrolysis, however, was not absorbed J Atheroscler

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Section: Ezetimibe and Ezetimibe/simvastatin In Combination With Fenomentioning

confidence: 99%

Section: Ezetimibe and Ezetimibe/simvastatin In Combination With Fenomentioning

confidence: 99%

Zetia: Inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to Reduce Intestinal Cholesterol Absorption and Treat Hyperlipidemia

Davis¹,

Veltri²

2007

J Atheroscler Thromb

145

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“…When added as monotherapy to patients currently receiving no cholesterol-lowering medication, ezetimibe has been shown to lower LDL-C by approximately 25-30 mg/ dl. 15,16 When added to or co-administered with ongoing atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, or rosuvastatin therapy, ezetimibe provides an additional 22-33 mg/dl decrease in LDL-C. [17][18][19][20][21][22][23][24][25][26][27] Therefore, we assumed that the addition of ezetimibe, either as monotherapy or as add-on therapy to the current cholesterol-lowering regimen, would provide an additional 25 mg/dl reduction in LDL-C, or a 2.5-step increase. The algorithm allowed us to predict the LDL-C2lowering regimen modification needed to attain the desired LDL-C goal.…”

Section: Methodsmentioning

confidence: 99%

Low-density lipoprotein cholesterol goal attainment in high-risk family medicine patients

Griend

Saseen

2009

Journal of Clinical Lipidology

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“…[6 -9] Also, coadministration of ezetimibe with statins could significantly reduce the risk of coronary heart disease (CHD) events in patients with hypercholesterolemia. [10] Atorvastatin (AT) ( Figure 1) is a selective, competitive inhibitor of HMGCoA reductase, the rate limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of the sterols, including cholesterol. It is used to reduce LDL cholesterol, apolipoprotein B, and triglycerides, and to increase HDL cholesterol in the treatment of hyperlipidaemias.…”

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confidence: 99%

HPLC Analysis for Simultaneous Determination of Atorvastatin and Ezetimibe in Pharmaceutical Formulations

Seshachalam¹,

Kothapally²

2008

Journal of Liquid Chromatography & Related Technologies

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A simple, isocratic, and sensitive reverse phase high performance liquid chromatographic (RP-LC) method has been developed, for the first time, for quantitative determination of atorvastatin and ezetimibe in pharmaceutical formulations. Atorvastatin and ezetimibe were chromatographed using 0.01 M ammonium acetate buffer (pH:3.0): Acetonitrile (50:50 v/v) as mobile phase. The detection was monitored at 254 nm. The retention times of ezetimibe and atorvastatin were 15.50 + 0.07 and 19.30 + 0.06, respectively. The linearity of the method was studied over the concentration range of 4 -400 mg/mL for atorvastatin and 5 -500 mg/mL for ezetimibe. The limit of detection for atorvastatin and ezetimibe were found as 1.25 mg/mL and 1.48 mg/mL, respectively. The proposed method was applied for the quantitative determination of atorvastatin and ezetimibe in commercial combination formulations.

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Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease

Cited by 47 publications

References 30 publications

Zetia: Inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to Reduce Intestinal Cholesterol Absorption and Treat Hyperlipidemia

Zetia: Inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to Reduce Intestinal Cholesterol Absorption and Treat Hyperlipidemia

Low-density lipoprotein cholesterol goal attainment in high-risk family medicine patients

HPLC Analysis for Simultaneous Determination of Atorvastatin and Ezetimibe in Pharmaceutical Formulations

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