Ezetimibe - A new approach in hypercholesterolemia management

Pharmacological Reports

Volumn 63, Issue 6, 2011, Pages 1335-1348

  Suchy, Dariusz ^a   Łabuzek, Krzysztof ^a   Stadnicki, Antoni ^a,b   Okopień, Bogusław ^a  

^a MEDICAL UNIVERSITY OF SILESIA   (Poland)

^b Department of Surgery District Hospital ^*  (Poland)

Author keywords

Ezetimibe; Hypercholesterolemia; Interactions; Pharmacokinetics

Indexed keywords

1,4 BIS(4 METHOXYPHENYL) 3 (3 PHENYLPROPYL) 2 AZETIDINONE; ANTIGEN; C REACTIVE PROTEIN; CARRIER PROTEINS AND BINDING PROTEINS; CHOLESTEROL; CYCLOSPORIN; CYTOCHROME P450; CYTOCHROME P450 3A4; DRUG METABOLITE; EZETIMIBE; FENOFIBRATE; FLUINDOSTATIN; GEMFIBROZIL; LEVOTHYROXINE; LOPINAVIR; LOW DENSITY LIPOPROTEIN; MEVINOLIN; MIPOMERSEN; NIEMANN PICK C1 LIKE 1 TRANSPORTER; PLACEBO; PRAVASTATIN; RHO KINASE; SIMVASTATIN; UNCLASSIFIED DRUG;

ANTIGEN EXPRESSION; ANTIINFLAMMATORY ACTIVITY; AREA UNDER THE CURVE; ATHEROSCLEROSIS; CARCINOGENICITY; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL TRANSPORT; DRUG ABSORPTION; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG EXCRETION; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG MEGADOSE; DRUG STRUCTURE; DRUG TARGETING; DRUG TRANSFORMATION; ENTEROHEPATIC CIRCULATION; ENZYME INHIBITION; ENZYME METABOLISM; GASTROINTESTINAL TRACT; GENETIC POLYMORPHISM; HEART GRAFT; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HYPERCHOLESTEROLEMIA; IMMUNOMODULATION; KIDNEY GRAFT; LIVER GRAFT; LOW DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; PLASMA CONCENTRATION-TIME CURVE; PROTEIN BLOOD LEVEL; PROTEIN TRANSPORT; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 84857490179     PISSN: 22995684     EISSN: 22995684     Source Type: Journal    
DOI: 10.1016/S1734-1140(11)70698-3     Document Type: Review

References (82)

1. Al Badarin FJ, Kullo IJ, Kopecky SL, Thomas RJ: Impact of ezetimibe on atherosclerosis: is the jury still out? Mayo Clin Proc, 2009, 84, 353-361.
2. Almutairi F, Peterson TC, Molinari M, Walsh MJ, Alwayn I, Peltekian KM: Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia. Liver Transpl, 2009, 15, 504-508.
3. Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP et al.: Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science, 2004, 303, 1201-1204. (Pubitemid 38233587)
4. Bennett MT, Johns KW, Bondy GP: Ezetimibe is effective when added to maximally tolerated lipid lowering therapy in patients with HIV. Lipids Health Dis, 2007, 6, 15.
5. Bergman AJ, Burke J, Larson P, Johnson-Levonas AO, Reyderman L, Statkevich P, Kosoglou T et al.: Effects of ezetimibe on cyclosporine pharmacokinetics in healthy subjects. J Clin Pharmacol, 2006, 46, 321-327. (Pubitemid 43260319)
6. Bergman AJ, Burke J, Larson P, Johnson-Levonas AO, Reyderman L, Statkevich P, Maxwell SE et al.: Interaction of single-dose ezetimibe and steady-state cyclosporine in renal transplant patients. J Clin Pharmacol, 2006, 46, 328-336. (Pubitemid 43260320)
7. Bilchick KC, Henrikson CA, Skojec D, Kasper EK, Blumenthal RS: Treatment of hyperlipidemia in cardiac transplant recipients. Am Heart J, 2004, 148, 200-210. (Pubitemid 39092785)
8. Chandra P, Brouwer KL: The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm Res, 2004, 21, 719-735. (Pubitemid 39011292)
9. Clader JW: The discovery of ezetimibe: a view from outside the receptor. J Med Chem, 2004, 47, 1-9.
10. Coll B, Aragonés G, Parra S, Alonso-Villaverde C, Masana L: Ezetimibe effectively decreases LDL-cholesterol in HIV-infected patients. AIDS, 2006, 20, 1675-1677. (Pubitemid 44162414)
11. 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, 80.
12. Crespo-Leiro MG, Paniagua MJ, Marzoa R, Grille Z, Naya C, Flores X, Rodriguez JA et al.: The efficacy and safety of ezetimibe for treatment of dyslipidemia after heart transplantation. Transplant Proc, 2008, 40, 3060-3062.
13. rd: An evaluation of rosuvastatin: pharmacokinetics, clinical efficacy and tolerability. Expert Opin Drug Metab Toxicol, 2008, 4, 287-304.
14. da Silva EF, Bárbaro G: New options in the treatment of lipid disorders in HIV-infected patients. Open AIDS J, 2009, 3, 31-37.
15. Dagli N, Yavuzkir M, Karaca I: The effects of high dose pravastatin and low dose pravastatin and ezetimibe combination therapy on lipid, glucose metabolism and inflammation. Inflammation, 2007, 30, 230-235. (Pubitemid 350264457)
16. Davidson MH: Ezetimibe: a novel option for lowering cholesterol. Expert Rev Cardiovasc Ther, 2003, 1, 11-21.
17. Davis HR Jr, Altmann SW: Niemann-Pick C1 Like 1 (NPC1L1) an intestinal sterol transporter. Biochim Biophys Acta, 2009, 1791, 679-683.
18. Drazen JM, D'Agostino RB, Ware JH, Morrissey S, Curfman GD: Ezetimibe and cancer - an uncertain association. N Engl J Med, 2008, 359, 1398-1399.
19. 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, 871-885. (Pubitemid 32554569)
20. Fleg JL, Mete M, Howard BV, Umans JG, Roman MJ, Ratner RE, Silverman A et al.: Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol, 2008, 52, 2198-2220.
21. Food and Drug Administration, USA. Zetia® (ezetimibe) Tablets label, 2008, 1-15 URL: http://www.accessdata.fda.gov/drugsatfda-docs/label/2008/ 021445s019lbl.pdf (Nov. 2009).
22. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH et al.: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci USA, 2005, 102, 8132-8137. (Pubitemid 40800055)
23. Garg A, Simha V: Update on dyslipidemia. J Clin Endocrinol Metab, 2007, 92, 1581-1589.
24. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K et al.: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos, 2004, 32, 314-320. (Pubitemid 38263889)
25. Gustavson LE, Schweitzer SM, Burt DA, Achari R, Rieser MJ, Edeki T, Chira T et al.: Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: A phase I, open-label, multiple-dose, three-period crossover study in healthy subjects. Clin Ther, 2006, 28, 373-387. (Pubitemid 43783438)
26. Halleck M, Davis HR, Kirschmeier P, Levitan D, Snyder RD, Treinen K, Macdonald JS: An assessment of the carcinogenic potential of ezetimibe using nonclinical data in a weight-of-evidence approach. Toxicology, 2009, 258, 116-130.
27. Hamilton-Craig I, Kostner K, Colquhoun D, Woodhouse S: At sea with SEAS: the first clinical endpoint trial for ezetimibe, treatment of patients with mild to moderate aortic stenosis, ends with mixed results and more controversy. Heart Lung Circ, 2009, 18, 343-346.
28. Hopkins PN: Familial hypercholesterolemia - improving treatment and meeting guidelines. Int J Cardiol, 2003, 89, 13-23.
29. Hosein S: Drug interactions. Kaletra and ezetimibe. Treatment Update, 2006, 18, 8.
30. Insull W Jr: Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J, 2006, 99, 257-273.
31. Jeu L, Cheng JW: Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor. Clin Ther, 2003, 25, 2352-2387. (Pubitemid 37267246)
32. John-Kalarickal J, Pearlman G, Carlson HE: New medications which decrease levothyroxine absorption. Thyroid, 2007, 17, 763-765. (Pubitemid 350194737)
33. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL et al.: Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med, 2008, 358, 1431-1443. (Pubitemid 351482735)
34. Kinlay S: Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol, 2007, 49, 2003-2009.
35. Kobashigawa JA, Starling RC, Mehra MR, Kormos RL, Bhat G, Barr ML, Sigouin CS et al.: Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients. J Heart Lung Transplant, 2006, 25, 1063-1069. (Pubitemid 44311519)
36. Kosoglou T, Ezzet F, Wexler D, Statkevich P: Influence of subject demographics on the pharmacokinetics of ezetimibe [abstract]. J Clin Pharmacol, 2004, 44, 1208.
37. Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, Mellars L et al.: Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol, 2002, 54, 309-319.
38. Kosoglou T, Statkevich P, Fruchart JC, Pember LJ, Reyderman L, Cutler DL, Guillaume M et al.: Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe. Curr Med Res Opin, 2004, 20, 1197-1207. (Pubitemid 39120784)
39. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet, 2005, 44, 467-494. (Pubitemid 40733733)
40. Kosoglou T, Statkevich P, Meyer I, Cutler DL, Musiol B, Yang B, Zhu Y et al.: Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin. Curr Med Res Opin, 2004, 20, 955-965. (Pubitemid 38821535)
41. Kosoglou T, Statkevich P, Yang B, Suresh R, Zhu Y, Boutros T, Maxwell SE et al.: Pharmacodynamic interaction between ezetimibe and rosuvastatin. Curr Med Res Opin, 2004, 20, 1185-1195. (Pubitemid 39120783)
42. Kramer W, Girbig F, Corsiero D, Pfenninger A, Frick W, Jähne G, Rhein M et al.: Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane. J Biol Chem, 2005, 280, 1306-1320.
43. Le VV, Racine N, Pelletier GB, Carrier M, Cossette M, White M: Impact of ezetimibe on cholesterol subfractions in dyslipidemic cardiac transplant recipients receiving statin therapy. Clin Transplant, 2009, 23, 249-255.
44. Liu PY, Liu YW, Lin LJ, Chen JH, Liao JK: Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation. Circulation, 2009, 119, 131-138.
45. López V, Gutiérrez C, Gutiérrez E, Sola E, Cabello M, Burgos D, González Molina M: Treatment with ezetimibe in kidney transplant recipients with uncontrolled dyslipidemia. Transplant Proc, 2008, 40, 2925-2926.
46. Mäki-Petäjä KM, Booth AD, Hall FC, Wallace SM, Brown J, McEniery CM, Wilkinson IB: Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol, 2007, 50, 852-858. (Pubitemid 47268750)
47. Negredo E, Moltó J, Puig J, Cinquegrana D, Bonjoch A, Pérez-Alvarez N, López-Blázquez R et al.: Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins. AIDS, 2006, 20, 2159-2164. (Pubitemid 44684706)
48. Okopień B, Kowalski J, Krysiak R, Łabuzek K, Stachura-Kułach A, Kułach A, Zieliński M, Herman ZS: Monocyte suppressing action of fenofibrate. Pharmacol Rep, 2005, 57, 367-372. (Pubitemid 41030697)
49. Orsó E, Werner T, Wolf Z, Bandulik S, Kramer W, Schmitz G: Ezetimib influences the expression of raft-associated antigens in human monocytes. Cytometry A, 2006, 69, 206-208.
50. Oswald S, Haenisch S, Fricke C, Sudhop T, Remmler C, Giessmann T, Jedlitschky G et al.: Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate- glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Clin Pharmacol Ther, 2006, 79, 206-217.
51. Oswald S, König J, Lütjohann D, Giessmann T, Kroemer HK, Rimmbach C, Rosskopf D et al.: Disposition of ezetimibe is influenced by polymorphisms of the hepatic uptake carrier OATP1B1. Pharmacogenet Genomics, 2008, 18, 559-568.
52. Parkinson A, Kazmi F, Buckley DB, Yerino P, Ogilvie BW, Paris BL: System-dependent outcomes during the evaluation of drug candidates as inhibitors of cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) enzymes: human hepatocytes versus liver microsomes versus recombinant enzymes. Drug Metab Pharmacokinet, 2010, 25, 16-27.
53. Patrick JE, Kosoglou T, Stauber KL, Alton KB, Maxwell SE, Zhu Y, Statkevich P et al.: Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos, 2002, 30, 430-437. (Pubitemid 34263828)
54. Pearson TA, Ballantyne CM, Veltri E, Shah A, Bird S, Lin J, Rosenberg E et al.: Pooled analyses of effects on C-reactive protein and low density lipoprotein cholesterol in placebo-controlled trials of ezetimibe monotherapy or ezetimibe added to baseline statin therapy. Am J Cardiol, 2009, 103, 369-374.
55. Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R: Analyses of cancer data from three ezetimibe trials. N Engl J Med, 2008, 359, 1357-1366.
56. Reyderman L, Kosoglou T, Boutros T, Seiberling M, Statkevich P: Pharmacokinetic interaction between ezetimibe and lovastatin in healthy volunteers. Curr Med Res Opin, 2004, 20, 1493-1500.
57. Reyderman L, Kosoglou T, Cutler DL, Maxwell S, Statkevich P: The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe. Curr Med Res Opin, 2005, 21, 1171-1179. (Pubitemid 41140720)
58. Reyderman L, Kosoglou T, Maxwell S, Chung C, Batra V, Statkevich P: Dose-proportionality of ezetimibe [abstract]. Clin Pharmacol Ther, 2002, 71, 97.
59. Reyderman L, Kosoglou T, Statkevich P, Pember L, Boutros T, Maxwell SE, Affrime M, Batra V: Assessment of a multiple-dose drug interaction between ezetimibe, a novel selective cholesterol absorption inhibitor and gemfibrozil. Int J Clin Pharmacol Ther, 2004, 42, 512-518. (Pubitemid 39255623)
60. Reyderman N, 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, 27.
61. Rodríguez-Ferrero ML, Anaya F: Ezetimibe in the treatment of uncontrolled hyperlipidemia in kidney transplant patients. Transplant Proc, 2008, 40, 3492-3495.
62. Rossebř AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E et al.: Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med, 2008, 359, 1343-1356.
63. Schulte S, Sukhova GK, Libby P: Genetically programmed biases in Th1 and Th2 immune responses modulate atherogenesis. Am J Pathol, 2008, 172, 1500-1508. (Pubitemid 351793344)
64. Seedorf U, Engel T, Lueken A, Bode G, Lorkowski S, Assmann G: Cholesterol absorption inhibitor ezetimibe blocks uptake of oxidized LDL in human macrophages. Biochem Biophys Res Commun, 2004, 320, 1337-1341. (Pubitemid 38916690)
65. Settergren M, Böhm F, Rydén L, Pernow J: Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J, 2008, 29, 1753-1760. (Pubitemid 352019812)
66. Shaw SM, Najam O, Khan U, Yonan N, Williams SG, Fildes JE: Ezetimibe and atorvastatin both immunoregulate CD4+ T cells from cardiac transplant recipients in vitro. Transpl Immunol, 2009, 21, 179-182.
67. Smart EJ, De Rose RA, Farber SA: Annexin 2-caveolin 1 complex is a target of ezetimibe and regulates intestinal cholesterol transport. Proc Natl Acad Sci USA, 2004, 101, 3450-3455. (Pubitemid 38338215)
68. Solomon KR, Pelton K, Boucher K, Joo J, Tully C, Zurakowski D, Schaffner CP et al.: Ezetimibe is an inhibitor of tumor angiogenesis. Am J Pathol, 2009, 174, 1017-1026.
69. Stamler J, Wentworth D, Neaton JD: Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA, 1986, 256, 2823-2828. (Pubitemid 17178359)
70. Stebbing J, Asghar AK, Holmes P, Bower M, Isenman HL, Nelson M: Use of ezetimibe during HIV infection. J Antimicrob Chemother, 2009, 63, 218-220.
71. Szkodziński J, Romanowski W, Hudzik B, Kaszuba A, Nowakowska-Zajdel E, Szkilnik R, Pietrasińska B et al.: Effect of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors on the concentration of insulin-like growth factor-1 (IGF-1) in hypercholesterolemic patients. Pharmacol Rep, 2009, 61, 654-664.
72. Taylor DO, Edwards LB, Boucek MM, Trulock EP, Aurora P, Christie J, Dobbels F et al.: Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult heart transplant report - 2007. J Heart Lung Transplant, 2007, 26, 769-781. (Pubitemid 47199081)
73. Türk TR, Voropaeva E, Kohnle M, Nürnberger J, Philipp T, Kribben A, Heemann U et al.: Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study. Nephrol Dial Transplant, 2008, 23, 369-373. (Pubitemid 351767400)
74. Uehara S, Chase CM, Colvin RB, Madsen JC, Russell PS: T-cell depletion eliminates the development of cardiac allograft vasculopathy in mice rendered tolerant by the induction of mixed chimerism. Transplant Proc, 2006, 38, 3169-3171. (Pubitemid 44908523)
75. van Loosdregt J, van Oosterhout MF, Bruggink AH, van Wichen DF, van Kuik J, de Koning E, Baan CC et al.: The chemokine and chemokine receptor profile of infiltrating cells in the wall of arteries with cardiac allograft vasculopathy is indicative of a memory T-helper 1 response. Circulation, 2006, 114, 1599-1607. (Pubitemid 44547430)
76. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA et al.: Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab, 2006, 4, 13-24. (Pubitemid 43942258)
77. Watanabe T, Kusuhara H, Maeda K, Shitara Y, Sugiyama Y: Physiologically based pharmacokinetic modeling to predict transporter-mediated clearance and distribution of pravastatin in humans. J Pharmacol Exp Ther, 2009, 328, 652-662.
78. Wohl DA, Waters D, Simpson RJ Jr: Ezetimibe alone reduces low-density lipoprotein cholesterol in HIV-infected patients receiving combination antiretroviral therapy. Clin Infect Dis, 2008, 47, 1105-1108.
79. Yoon HE, Song JC, Hyoung BJ, Hwang HS, Lee SY, Jeon YJ, Choi BS et al.: The efficacy and safety of ezetimibe and low-dose simvastatin as a primary treatment for dyslipidemia in renal transplant recipients. Korean J Intern Med, 2009, 24, 233-237.
80. Yu RZ, Geary RS, Flaim JD, Riley GC, Tribble DL, vanVliet AA, Wedel MK: Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2′-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Clin Pharmacokinet, 2009, 48, 39-50.
81. Zhu Y, Statkevich P, Kosoglou T, Maxwell SE, Anderson L, Patrick JE, Batra V: Lack of pharmacokinetic interaction between ezetimibe and atorvastatin [abstract]. Clin Pharmacol Ther, 2001, 69, P68.
82. Zhu Y, Statkevich P, Kosoglou T, Zambas D, Patrick JE, Cayen MN, Batra V: Effect of ezetimibe (SCH 58235) on the activity of drug metabolizing enzymes in vivo [abstract]. Clin Pharmacol Ther, 2000, 67, 152.