The potent cholesterol absorption inhibitor, ezetimibe, is glucuronidated in the intestine, localizes to the intestine, and circulates enterohepatically

Heek, Margaret van; Farley, Constance; Compton, Douglas S; Hoos, Lizbeth; Alton, Kevin B.; Sybertz, Edmund J.; Davis, Harry R.

doi:10.1016/s0021-9150(00)80703-0

Cited by 15 publications

(14 citation statements)

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“…1), (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidine-2-one is a selective cholesterol absorbtion inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol (Van Heek et al, 1997) from the small intestine without affecting the absorption of fat-soluble vitamins, triglyceride or bile acids. Clinical studies have shown that co-administration of ezetimibe with statins could provide significant reductions in both the low-density lipoproteins (LDL) and the total cholesterol with slight increase in the high-density lipoproteins (HDL) (Ballantyne et al, 2003;Davidson et al, 2002;Kerzner et al, 2003;Melani et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Chemometric technique for the optimization of chromatographic system: Simultaneous HPLC determination of Rosuvastatin, Telmisartan, Ezetimibe and Atorvastatin used in combined cardiovascular therapy

Janardhanan

Manavalan

Valliappan

2016

Arabian Journal of Chemistry

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Developed and optimized a validated isocratic reverse phase HPLC separation of Rosuvastatin, Telmisartan, Ezetimibe and Atorvastatin in pharmaceutical preparation using response surface methodology. The separation was carried out by using phenomenex C 18 column (15 cm · 4.6 mm id, 5 lm particle size) and UV detection at 239 nm. The ranges of the independent variables used for the optimization were MeCN: 33-38%, buffer conc.: 10-20 mM and flow rate: 1-2 ml/min. The influence of these independent variables on the output responses: capacity factor of the first peak (k 1 ), resolutions of the 2nd and 3rd peak (Rs 2,3 ), and capacity factor of the fifth peak (k 5 ) were evaluated. Using this strategy, a mathematical model was defined and a response surface was derived for the separation. The three responses were simultaneously optimized by using Derringer's desirability functions. Optimum conditions chosen for the assay were MeCN, MeOH, 20 mM K 2 HPO 4 (pH 3.0 ± 0.2) solution (34.27:20:45.73 v/v/v) and flow rate 2 ml/min. Total chromatographic analysis time per sample was approximately 10 min. The optimized assay condition was validated as per the ICH guidelines and applied for the quantitative analysis of Rosavel EZ, Avas-EZ and Lipisar 20 tablet. The developed method was simple, accurate and precise. Hence, it can be employed for the routine analysis in quality control laboratories.

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Section: Introductionmentioning

confidence: 99%

Chemometric technique for the optimization of chromatographic system: Simultaneous HPLC determination of Rosuvastatin, Telmisartan, Ezetimibe and Atorvastatin used in combined cardiovascular therapy

Janardhanan

Manavalan

Valliappan

2016

Arabian Journal of Chemistry

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“…The structure of the compound is shown in Figure 5. Data obtained in bile duct cannulated rats shows that SCH-58235 is glucuronidated in the intestine and undergoes enterohepatic circulation, the glucuronide being a more efficient inhibitor of cholesterol absorption than the parent compound [20]. A randomised, double-blind, placebo-controlled trial compared the effect on serum lipids, with doses ranging from 0.25 -10 mg once daily with placebo in 243 hypercholesterolaemic subjects over a period of 12 weeks [21].…”

Section: Ezetimibe (Sch-58235 Schering-plough Research Institute Usa)mentioning

confidence: 99%

Novel lipid-regulating drugs

Thompson

Naoumova

2000

Expert Opinion on Investigational Drugs

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This review describes the major developments in lipid-regulating drugs during the past two years. Most of the novel compounds that have been launched or were in their final stages of development during this period are aimed primarily at lowering low-density lipoprotein (LDL)-cholesterol. These include bile acid sequestrants, HMG-CoA reductase inhibitors and a cholesterol absorption inhibitor. In addition, there have been preclinical reports suggesting the potential usefulness of orally bioavailable inhibitors of cholesterol ester transfer protein in plasma and of acylcoA:cholesterol acyltransferase in monocyte-macrophages. The recent discovery of the roles of the scavenger receptor class B Type 1 and ATP-binding cassette transporter 1 in high-density lipoprotein (HDL)-cholesterol transport may shift the trend of future developments away from compounds that lower LDL to those aimed at promoting HDL turnover.

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“…One can expect, therefore, that fluorine-containing b-lactams will serve as important and useful bioactive compounds for medicinal chemistry and chemical biology. For example, Ezetimibe, a blactam containing fluorine in the side chain, is the first of the selective cholesterol absorption inhibitors [11]. b-Lactams bearing a fluorine atom in the alpha position of the side chain have been intensively investigated as potential antibiotics [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

A simple route to side-chain fluorinated β-lactams from ring-fluorinated aziridines

Konev

Новиков

Khlebnikov

et al. 2007

Journal of Fluorine Chemistry

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The potent cholesterol absorption inhibitor, ezetimibe, is glucuronidated in the intestine, localizes to the intestine, and circulates enterohepatically

Cited by 15 publications

References 0 publications

Chemometric technique for the optimization of chromatographic system: Simultaneous HPLC determination of Rosuvastatin, Telmisartan, Ezetimibe and Atorvastatin used in combined cardiovascular therapy

Chemometric technique for the optimization of chromatographic system: Simultaneous HPLC determination of Rosuvastatin, Telmisartan, Ezetimibe and Atorvastatin used in combined cardiovascular therapy

Novel lipid-regulating drugs

A simple route to side-chain fluorinated β-lactams from ring-fluorinated aziridines

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