Ezetimibe for management of hypercholesterolemia

Annals of Pharmacotherapy

Volumn 37, Issue 6, 2003, Pages 839-848

  Mauro, Vincent F ^a,b   Tuckerman, Chad E ^b  

^a UNIVERSITY OF TOLEDO   (United States)

^b MEDICAL COLLEGE OF OHIO   (United States)

Author keywords

2 azetidinone; Ezetimibe; Hypercholesterolemia

Indexed keywords

1,4 BIS(4 METHOXYPHENYL) 3 (3 PHENYLPROPYL) 2 AZETIDINONE; 2 AZETIDINONE DERIVATIVE; ATORVASTATIN; CAFFEINE; CAMPESTEROL; CIMETIDINE; COLESTYRAMINE; DAPSONE; DEXTROMETHORPHAN; DIGOXIN; EZETIMIBE; FENOFIBRATE; FLUINDOSTATIN; GEMFIBROZIL; GLIPIZIDE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; MIDAZOLAM; ORAL CONTRACEPTIVE AGENT; PLACEBO; PRAVASTATIN; SCH 60663; SIMVASTATIN; SITOSTEROL; STATINE; TOLBUTAMIDE; TRIACYLGLYCEROL; UNINDEXED DRUG; WARFARIN;

ABDOMINAL DISCOMFORT; ARTHRALGIA; CARDIOVASCULAR DISEASE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG HALF LIFE; DRUG STRUCTURE; DRUG TOLERABILITY; DYSGEUSIA; EDEMA; FATIGUE; FLATULENCE; HEADACHE; HUMAN; HYPERCHOLESTEROLEMIA; MEDLINE; META ANALYSIS; METABOLIC DISORDER; MYALGIA; NIGHTMARE; PHARYNGITIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; REVIEW; SINUSITIS; SITOSTEROLEMIA; THORAX PAIN; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; VERTIGO; WRIST DISEASE;

ANIMALS; AZETIDINES; CLINICAL TRIALS; DISEASE MANAGEMENT; HUMANS; HYPERCHOLESTEROLEMIA;

EID: 0038823934     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1C209     Document Type: Review

References (64)

1. 2002 Heart and stroke statistical update. Dallas, TX: American Heart Association, 2001.
2. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel of Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
3. Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol 1997;80:106-7.
4. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Scandinavian Simvastatin Survival Study Group. Lancet 1994;344:1383-9.
5. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW. et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-7.
6. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-64.
7. Illingworth DR. New horizons in combination drug therapy for hypercholesterolemia. Cardiology 1989:76(suppl 1):83-100.
8. Burnett DA, Caplen MA, Davis HR, Burrier RE, Clader JW. 2-Azetidinones as inhibitors of cholesterol absorption. J Med Chem 1994;37: 1733-6.
9. Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol 2002;54: 309-19.
10. Statkevich P, Reyderman L, Kosoglou T, Woloj M, Maxwell SE, Cutler DL, et al. Ezetimibe does not affect the pharmacokinetics and pharmacodynamics of glipizide (abstract). Clin Pharmacol Ther 2001;69:P67.
11. Keung ACF, Kosoglou T, Statkevich P, Anderson L, Boutros T, Cutler DL, et al. Ezetimibe does not affect the pharmacokinetics of oral contraceptives (abstract). Clin Pharmacol Ther 2001;69:P55.
12. Bauer KS, Kosoglou T, Statkevich P, Calzetta A, Maxwell SE, Patrick JE, et al. Ezetimibe does not affect the pharmacokinetics or pharmacodynamics of warfarin (abstract). Clin Pharmacol Ther 2001;69:P5.
13. Kosoglou T, Statkevich P, Bauer KS, Cutler DL, Maxwell SE, Soni PP, et al. Ezetimibe does not affect the pharmacokinetics and pharmacodynamics of digoxin (abstract). American Association of Pharmaceutical Scientists Annual Meeting Supplement [serial online] 2001;3(3).www.aapspharmaceutica.com (accessed 2002 Aug 22).
14. van Heek M, Farley C, Compton DS, Hoos L, Davis HR. Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function. Br J Pharmacol 2001;134:409-17.
15. Knopp RH, Bays H, Manion CV, Lipka LJ, Melani L, LeBeaut AP, et al. Effect of ezetimibe on serum concentrations of lipid-soluble vitamins (abstract). Atherosclerosis Suppl 2001;2:90.
16. Product pipeline: worldwide ethical products. Kenilworth, NJ: Schering-Plough Corporation, July 2002.
17. Package information. Zetia (ezetimibe). North Wales, PA: Merck/ Schering-Plough Pharmaceuticals, October 2002.
18. van Heek M, France CF, Compton DS, McLeod RL, Yumibe NP, Alton KB, et al. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor. SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 1997;283:157-63.
19. Vaccaro WD, Davis HR. Sugar-substituted 2-azetidinone cholesterol absorption inhibitors: enhanced potency by modification of the sugar. Bioorg Med Chem Lett 1998;8:313-8.
20. Rosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe N, Clader JW, et al. Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)- (4-hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption. J Med Chem 1998;41:973-80.
21. Burrier R, Smith A, McGregor D, Hoos L, Sybertz E, Davis H. Effect of SCH48461 on intestinal cholesterol metabolism in the hamster (abstract). Atherosclerosis 1994;109:163.
22. Sliskovic DR, White AD. Therapeutic potential of ACAT inhibitors as lipid lowering and anti-atherosclerotic agents. Trends Pharmacol Sci 1991;12:194-9.
23. Shepherd J. The role of the exogenous pathway in hypercholesterolaemia. Eur Heart J Suppl 2001;3(suppl E):E2-5.
24. Clader JW, Burnett DA, Caplen MA, Domalski MS, Dugar S, Vaccaro W, et al. 2-Azetidinone cholesterol absorption inhibitors: structure-activity relationships on the heterocyclic nucleus. J Med Chem 1996;39: 3684-93.
25. Salisbury BG, Davis HR, Burrier RE, Burnett DA, Boykow G, Caplen MA, et al. Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461. Atherosclerosis 1995;115:45-63.
26. Hauser H, Dyer JH, Nandy A, Vega MA, Werder M, Bieliauskaite E, et al. Identification of a receptor mediating absorption of dietary cholesterol in the intestine. Biochemistry 1998;37:17843-50.
27. Hernandez M, Montenegro J, Steiner M, Kim D, Sparrow C, Detmers PA, et al. Intestinal absorption of cholesterol is mediated by a saturable, inhibitable transporter. Biochim Biophys Acta 2000;1486:232-42.
28. Turley SD. Dietary cholesterol and the mechanisms of cholesterol absorption. Eur Heart J Suppl 1999;1(suppl S):S29-35.
29. Kramer W, Glombik H, Petry S, Heuer H, Schafer H, Wendler W, et al. Identification of binding proteins for cholesterol absorption inhibitors as components of the intestinal cholesterol transporter. FEBS Lett 2000; 487:293-7.
30. Davis HR, Pula KK, Alton KB, Burrier RE, Watkins RW. The synergistic hypocholesterolemic activity of the potent cholesterol absorption inhibitor, ezetimibe, in combination with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in dogs. Metabolism 2001;50:1234-41.
31. von Bergmann K, Salen G, Lutjohann D, Musliner T, Musser B. Ezetimibe effectively reduces serum plant sterols in patients with sitosterolemia (abstract). Presented at: 73rd European Atherosclerosis Society Congress, Salzburg, Austria, July 2002. www.kenes.com/73eas/program/abstracts/ 405.doc (accessed 2002 Oct 4).
32. Ezzet F, Krishna G, Wexler DB, Statkevich P, Kosoglou T, Batra VK. A population pharmacokinetic model that describes multiple peaks due to enterohepatic recirculation of ezetimibe. Clin Ther 2001;23:871-85.
33. van Heek M, Farley C, Compton DS, Hoos L, Alton KB, Sybertz EJ, et al. Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663. Br J Pharmacol 2000;129:1748-54.
34. Patrick JE, Kosoglou T, Stauber KL, Alton KB, Maxwell SE, Zhu Y, et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos 2002;30:430-7.
35. Courtney RD, Kosoglou T, Statkevich P, Boutros T, Maxwell SE, Batra VK. Effect of food on the oral bioavailability of ezetimibe (abstract). Clin Pharmacol Ther 2002;71:P80.
36. Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA, et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther 2001;23:1209-30.
37. Stein E. Results of phase I/II clinical trials with ezetimibe, a novel selective cholesterol absorption inhibitor. Eur Heart J Suppl 2001;3 (suppl E):E11-6.
38. Zhu Y, Statkevich P, Kosoglou T, Boutros T, Maxwell SE, Patrick J, et al. Effect of age on the pharmacokinetics of ezetimibe (abstract). American Association of Pharmaceutical Scientists Annual Meeting Supplement [serial online] 2000;2(4). www.aapspharmaceutica.com (accessed 2002 Aug 22).
39. Ezzet F, Wexler D, Statkevich P, Kosoglou T, Patrick J, Lipka L, et al. The plasma concentration and LDL-C relationship in patients receiving ezetimibe. J Clin Pharmacol 2001;41:943-9.
40. Kosoglou T, Kakkar T, Statkevich P, Anderson L, Pai S, Boutros T, et al. Multiple-dose safety and pharmacokinetics of ezetimibe in adolescent children (abstract). Clin Pharmacol Ther 2001;69:P52
41. van Heek M, Compton DS, Davis HR. The cholesterol absorption inhibitor, ezetimibe, decreases diet-induced hypercholesterolemia in monkeys. Eur J Pharmacol 2001;415:79-84.
42. Reyderman L, Kosoglou T, Statkevich P, Pember L, Maxwell S, Batra V. Pharmacokinetics of ezetimibe in subjects with normal renal function or severe chronic renal insufficiency (abstract). Clin Pharmacol Ther 2002; 71:P27.
43. Sudhop T, Lutjohann D, Kodal A, Igel M, Tribble DL, Shah S, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002;106:1943-8.
44. Dujovne CA, Ettinger MP. McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol 2002;90:1092-7.
45. Kosoglou T, Seiberling M, Statkevich P, Cutler DL, Yang B, Anderson L, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and atorvastatin (abstract). J Am Coll Cardiol 2001;37(suppl A):229A.
46. Kosoglou T, Meyer I, Musiol B, Anderson L, Reyderman L, Statkevich P, et al. Pharmacodynamic interaction between fluvastatin and ezetimibe has favorable clinical implications (abstract). Atherosclerosis Suppl 2001;2:89.
47. Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 2002;90:1084-91.
48. Davidson MH, McGarry T, Bettis R, Melani L, Lipka U, LeBeaut AP, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002;40:2125-34.
49. Ballantyne C, Houri J, Notarbartolo A, Melani L, Lipka L, LeBeaut A, et al. Ezetimibe co-administered with atorvastatin in 628 patients with primary hypercholesterolemia (abstract). J Am Coll Cardiol 2002;39(suppl A):227A.
50. Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al. Ezetimibe co-administered with pravastatin in 538 patients with primary hypercholesterolemia (abstract). J Am Coll Cardiol 2002;39(suppl B):134B.
51. Lipka L, Kerzner B, Corbelli J, Sharp S, Melani L, LeBeaut A, et al. Results of ezetimibe co-administered with lovastatin in 548 patients with primary hypercholesterolemia (abstract). J Am Coll Cardiol 2002;39 (suppl B):430B.
52. Kosoglou T, Guillaume M, Sun S, Pember LJC, Reyderman L, Statkevich P, et al. Pharmacodynamic interaction between fenofibrate and the cholesterol absorption inhibitor ezetimibe (abstract). Atherosclerosis Suppl 2001;2:38.
53. Bilheimer DW, Grundy SM, Brown MS, Goldstein JL. Mevinolin and colestipol simulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci U S A 1983;80:4124-8.
54. Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic & molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001: 2863-913.
55. Postiglione A, Montefusco S, Pauciullo P, Mancini M, Piliego T. Effects of atorvastatin in patients with homozygous familial hypercholesterolemia (letter). Atherosclerosis 1999;147:423-4.
56. Raal FJ, Pilcher GJ, Illingworth DR, Pappu AS, Stein EA, Laskarzewski P, et al. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis 1997;135:249-56.
57. Gagne C, Gaudet D, Bruckert E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 2002;105:2469-75.
58. Bjorkhem I, Boberg KM, Leitersdorf E. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic & molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2961-88.
59. Zhu Y, Statkevich P, Kosoglou T, Zambas D, Patrick J, Cayen MN, et al. Effect of SCH 58235 on the activity of drug metabolizing enzymes in vivo (abstract). Clin Pharmacol Ther 2000;67:152.
60. Statkevich P, Zhu Y, Kosoglou T, Affrime MB, Salfi M, Patrick J, et al. SCH 58235 does not affect the pharmacokinetics of simvastatin (abstract). Clin Pharmacol Ther 2000;67:146.
61. Krishna G, Kosoglou T, Ezzet F, Pember L, Statkevich P, Boutros T, et al. Effect of cimetidine on the pharmacokinetics of ezetimibe (abstract). American Association of Pharmaceutical Scientists Annual Meeting Supplement [serial online] 2001;3(3). www.aapspharmaceutica.com (accessed 2002 Aug 22).
62. Courtney RD, Kosoglou T, Statkevich P, Boutros T, Maxwell SE, Pember L, et al. Effect of antacid on the pharmacokinetics of ezetimibe (abstract). Clin Pharmacol Ther 2002;71:P80.
63. LoBuono C. Lipid-lowering drug marks first new class in 15 years. Drug Topics 2002:146(Nov 18):19.
64. Sotiriou CG, Cheng JWM. Beneficial effects of statins in coronary artery disease - beyond lowering cholesterol. Ann Pharmacother 2000;34: 1432-9. DOI 10.1345/aph.10124