Current status of CETP inhibitors in the treatment of hyperlipidemia: An update

Current Clinical Pharmacology

Volumn 7, Issue 2, 2012, Pages 102-110

  Ghosh, Raktim Kumar ^a   Ghosh, Samhati Mondal ^b  

^a MAULANA AZAD MEDICAL COLLEGE   (India)

^b ALL INDIA INSTITUTE OF MEDICAL SCIENCES   (India)

Author keywords

Anacetrapib; CETP inhibitors; Dalcetrapib; HDL cholesterol; Reverse cholesterol transport; Torcetrapib

Indexed keywords

ALDOSTERONE; ANACETRAPIB; ATORVASTATIN; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; DALCETRAPIB; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; MOXIFLOXACIN; OUABAIN; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; TORCETRAPIB;

ADRENALECTOMY; BLOOD PRESSURE; CHOLESTEROL TRANSPORT; FOLLOW UP; HUMAN; HYPERLIPIDEMIA; METABOLIC SYNDROME X; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; QT PROLONGATION; REVIEW;

EID: 84860505430     PISSN: 15748847     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488412800228884     Document Type: Review

References (41)

1. Niesor EJ. Different effects of compounds decreasing cholesteryl ester transfer protein activity on lipoprotein metabolism. Curr Opin Lipidol 2011 May 16. [Epub ahead of print]
2. Masson D, Jiang XC, Lagrost L, Tall AR. The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis. J Lipid Res 2009; 50(Suppl): S201-6.
3. Yamashita S, Hirano K, Sakai N, Matsuzawa Y. Molecular biology and pathophysiological aspects of plasma cholesteryl ester transfer protein. Biochim Biophys Acta. 2000; 1529: 257-75.
4. Davidson MH. Update on CETP inhibition. J Clin Lipidol 2010; 4: 394-8.
5. Hesler CB, Swenson TL, Tall AR. Purification and characterization of a human plasma cholesteryl ester transfer protein. J Biol Chem 1987; 262: 2275-82.
6. Yamashita S, Sakai N, Hirano K, et al. Roles of plasma lipid transfer proteins in reverse cholesterol transport. Front Biosci 2001; 6: D366-87.
7. Nagano M, Yamashita S, Hirano K, et al. Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese. J Atheroscler Thromb 2004; 11: 110-21.
8. Ranalletta M, Bierilo KK, Chen Y, et al. Biochemical characterization of cholesteryl ester transfer protein inhibitors. J Lipid Res 2010; 51: 2739-52.
9. Rensen PC, Havekes LM. Cholesteryl ester transfer protein inhibition: effect of reverse cholesterol transport? Arterioscler Thromb Vasc Biol 2006; 26: 681-684
10. Barter P. Lessons learned from the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Am J Cardiol 2009; 104: 10E-5E.
11. Funder JW. Aldosterone, hypertension and heart failure: insights from clinical trials Hypertens Res 2010; 33: 872-5.
12. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357: 2109-22
13. Joy T, Hegele RA. The end of the road for CETP inhibitors after torcetrapib? Curr Opin Cardiol 2009; 24: 364-71.
14. Neeli H, Rader DJ. Cholesteryl ester transfer protein (CETP) inhibitors: is there life after torcetrapib? Cardiol Clin 2008; 26: 537-46.
15. Kuhlmann O, Heinig K. Dalcetrapib pharmacokinetics and metabolism in the cynomolgus monkey. Xenobiotica 2011; 41: 430-6.
16. Perez A, Wright MB, Maugeais C, et al. MARCO, a macrophage scavenger receptor highly expressed in rodents, mediates dalcetrapib-induced uptake of lipids by rat and mouse macrophages. Toxicol In Vitro 2010; 24: 745-50.
17. Stroes ES, Kastelein JJ, Bénardeau A, et al. Dalcetrapib: no offtarget toxicity on blood pressure or on genes related to the reninangiotensin-aldosterone system in rats. Br J Pharmacol 2009; 158: 1763-70.
18. Derks M, Anzures-Cabrera J, Turnbull L, Phelan M. Safety, tolerability and pharmacokinetics of dalcetrapib following single and multiple ascending doses in healthy subjects: a randomized, double-blind, placebo-controlled, phase I study. Clin Drug Investig 2011; 31: 325-35.
19. Schwartz GG, Olsson AG, Ballantyne CM, Barter PJ, Holme IM, Kallend D, Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009; 158: 896-901.
20. Robinson JG. Dalcetrapib: a review of Phase II data. Expert Opin Investig Drugs 2010; 19: 795-805.
21. Kastelein JJ, Duivenvoorden R, Deanfield J, et al. Rationale and design of dal-VESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flowmediated vasodilatation. Curr Med Res Opin 2011; 27(1): 141-50.
22. Stein EA, Stroes ES, Steiner G, et al. Safety and tolerability of dalcetrapib. Am J Cardiol 2009; 104: 82-91.
23. Stein EA, Roth EM, Rhyne JM, Burgess T, Kallend D, Robinson JG. Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial. Eur Heart J 2010; 31: 480-8.
24. Derks M, Abt M, Phelan M. Lack of clinically relevant drug-drug interactions when dalcetrapib is co-administered with ezetimibe. Br J Clin Pharmacol 2010; 70: 825-33.
25. Derks M, Abt M, Parr G, Meneses-Lorente G, Young AM, Phelan M. No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin. Expert Opin Investig Drugs 2010; 19: 1135-45.
26. Derks M, Abt M, Phelan M, et al. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions. J Clin Pharmacol 2010; 50: 1188-201.
27. Derks M, Abt M, Mwangi A, Meneses-Lorente G. Lack of effect of dalcetrapib on QT interval in healthy subjects following multiple dosing. Eur J Clin Pharmacol 2010; 66: 775-83.
28. Stalenhoef AF, Robinson JG, Burgess T, et al. Efficacy and safety of dalcetrapib in type 2 diabetes mellitus and/or metabolic syndrome patients, at high cardiovascular disease risk. Diabetes Obes Metab 2012; 14(1): 30-9.
29. Tchoua U, D'Souza W, Mukhamedova N, et al. The effect of cholesteryl ester transport protein overexpression and inhibition on reverse cholesterol transport. Cardiovasc Res 2008; 77: 732-39.
30. Natarajan P, Ray KK, Cannon CP. High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol 2010; 55: 1283-99.
31. Hunt JA, Lu Z. Cholesteryl ester transfer protein (CETP) inhibitors. Curr Top Med Chem 2009; 9: 419-27.
32. Miyares MA. Anacetrapib and dalcetrapib: two novel cholesteryl ester transfer protein inhibitors. Ann Pharmacother 2011; 45: 84-94.
33. Tan EY, Hartmann G, Chen Q, et al. Pharmacokinetics, metabolism, and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in rats and rhesus monkeys. Drug Metab Dispos 2010; 38: 459-73.
34. Krishna R, Garg A, Panebianco D, et al. Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Br J Clin Pharmacol 2009; 68: 535-45.
35. Krishna R, Anderson MS, Bergman AJ, et al. Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet 2007; 370: 1907-14.
36. Cannon CP, Dansky HM, Davidson M, et al. Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib. Am Heart J 2009; 158: 513-519.
37. Krishna R, Bergman AJ, Jin B, et al. Assessment of the CYP3A-mediated drug interaction potential of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy volunteers. J Clin Pharmacol 2009; 49: 80-7.
38. Kumar S, Tan EY, Hartmann G, et al. Metabolism and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in humans. Drug Metab Dispos 2010; 38: 474-83.
39. Bloomfield D, Carlson GL, Sapre A, et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J 2009; 157: 352-360.
40. Krishna R, Garg A, Jin B, et al. Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Br J Clin Pharmacol 2009; 67: 520-6
41. Krishna R, Bergman AJ, Green M, Dockendorf MF, Wagner JA, Dykstra K. Model-based development of anacetrapib, a novel cholesteryl ester transfer protein inhibitor. AAPS J 2011; 13: 179-90.