Analysis of "on/Off" Kinetics of a CETP Inhibitor Using a Mechanistic Model of Lipoprotein Metabolism and Kinetics

CPT: Pharmacometrics and Systems Pharmacology

Volumn 4, Issue 8, 2015, Pages 465-473

  Lu, J ^a   Cleary, Y ^a   Maugeais, C ^a   Kiu Weber, C I ^a   Mazer, N A ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTILIPEMIC AGENT; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; RG 7232; UNCLASSIFIED DRUG;

ARTICLE; CALIBRATION; CHOLESTEROL TRANSPORT; COMPARTMENT MODEL; DOSE RESPONSE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; ENZYME INHIBITION; HUMAN; HUMAN EXPERIMENT; LIPOPROTEIN METABOLISM; MALE; NORMAL HUMAN; OSCILLATION; PLASMA HALF LIFE; PRIORITY JOURNAL; VALIDATION STUDY;

EID: 84936978314     PISSN: None     EISSN: 21638306     Source Type: Journal    
DOI: 10.1002/psp4.27     Document Type: Article

References (36)

1. Kingwell, B.A., Chapman, M.J., Kontush, A., Miller, N.E. HDL-targeted therapies: progress, failures and future. Nat. Rev. Drug. Discov. 13, 445-464 (2014).
2. Rosenson, R.S. et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125, 1905-1919 (2012).
3. Mackey, R.H., Greenland, P., Goff, D.C., Lloyd-Jones, D., Sibley, C.T., Mora, S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J. Am. Coll. Cardiol. 60, 508-516 (2012).
4. Hubner, K., Schwager, T., Winkler, K., Reich, J.G., Holzhutter, H.G. Computational lipidology: predicting lipoprotein density profiles in human blood plasma. PLoS Comput. Biol. 4, 1000079 (2008).
5. de Graaf, A.A., van Schalkwijk, D.B. Computational models for analyzing lipoprotein profiles. Clin. Lipidol. 6, 25-33 (2011).
6. Hersberger, M., von Eckardstein, A. Modulation of high-density lipoprotein cholesterol metabolism and reverse cholesterol transport. Handb. Exp. Pharmacol. 170, 537-561 (2005).
7. Rader, D.J., Tall, A.R. The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis Nat. Med. 18, 1344-1346 (2012).
8. Friedrich, S., Kastelein, J.J., James, D., Waterhouse, T., Nissen, S.E., Nicholls, S.J., Krueger, K.A. The pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of evacetrapib administered as monotherapy or in combination with statins. CPT Pharmacometrics Syst. Pharmacol. 3, 94 (2014).
9. Gieschke, R., Serafin, D. Development of Innovative Drugs via Modeling with MATLAB: A Practical Guide (Springer, Berlin Heidelberg, 2013).
10. Lu, J., Mazer, N.A., Hubner, K. Mathematical models of lipoprotein metabolism and kinetics-current status and future perspectives. Clin. Lipidol. 8, 595-604 (2013).
11. Wahba, K., Lo, A., Kadambi, A., Powell, L.M. Clinical trial simulations of dyslipidemic patients in a mechanistic model of cardiovascular disease predict little impact on CHD events by CETP inhibitors. Circulation 124, 9560 (2011).
12. Lu, J., Hubner, K., Nanjee, M.N., Brinton, E.A., Mazer, N.A. An in-silico model of lipoprotein metabolism and kinetics for the evaluation of targets and biomarkers in the reverse cholesterol transport pathway. PLoS Comput. Biol. 10, 1003509 (2014).
13. Siebel, A.L. et al. Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion. Circ. Res. 113, 167-175 (2013).
14. de Grooth, G.J., Klerkx, A.H., Stroes, E.S., Stalenhoef, A.F., Kastelein, J.J., Kuivenhoven, J.A. A review of CETP and its relation to atherosclerosis. J. Lipid. Res. 45, 1967-1974 (2004).
15. Rye, K.A., Clay, M.A., Barter, P.J. Remodelling of high density lipoproteins by plasma factors. Atherosclerosis 145, 227-238 (1999).
16. Kunitake, S.T., La Sala, K.J., Kane, J.P. Apolipoprotein A-I-containing lipoproteins with pre-beta electrophoretic mobility. J. Lipid. Res. 26, 549-555 (1985).
17. Nanjee, M.N., Brinton, E.A. Very small apolipoprotein A-I-containing particles from human plasma: isolation and quantification by high-performance size-exclusion chromatography. Clin. Chem. 46, 207-223 (2000).
18. Tall, A.R., Yvan-Charvet, L., Wang, N. The failure of torcetrapib: was it the molecule or the mechanism Arterioscler. Thromb. Vasc. Biol. 27, 257-260 (2007).
19. Tall, A.R. The effects of cholesterol ester transfer protein inhibition on cholesterol efflux. Am. J. Cardiol. 104(10 Suppl), 39-45 (2009).
20. Niesor, E.J. et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-b-HDL formation and increases reverse cholesterol transport. J. Lipid. Res. 51, 3443-3454 (2010).
21. Niesor, E.J. Different effects of compounds decreasing cholesteryl ester transfer protein activity on lipoprotein metabolism. Curr. Opin. Lipidol. 22, 288-295 (2011).
22. Hooper, A.J., Burnett, J.R. Anacetrapib, a cholesteryl ester transfer protein inhibitor. Expert. Opin. Investig. Drugs 21, 103-109 (2012).
23. Nigon, F., Lesnik, P., Rouis, M., Chapman, M.J. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J. Lipid. Res. 32, 1741-1753 (1991).
24. Chappell, D.A., Fry, G.L., Waknitz, M.A., Berns, J.J. Ligand size as a determinant for catabolism by the low density lipoprotein (LDL) receptor pathway. A lattice model for LDL binding. J. Biol. Chem. 266, 19296-19302 (1991).
25. Jeyarajah, E.J., Cromwell, W.C., Otvos, J.D. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin. Lab. Med. 26, 847-870 (2006).
26. Maugeais, C. et al. A minimal model using stable isotopes to study the metabolism of apolipoprotein B-containing lipoproteins in humans. Diabetes Metab 22, 57-63 (1996).
27. Aster, R., Borchers, B., Thurber, C. Parameter Estimation and Inverse Problems (Academic Press, Burlington, MA, 2005).
28. Mazer, N.A., Giulianini, F., Paynter, N.P., Jordan, P., Mora, S. A comparison of the theoretical relationship between HDL size and the ratio of HDL cholesterol to apolipoprotein A-I with experimental results from the Women's Health Study. Clin. Chem. 59, 949-958 (2013).
29. Tall, A.R., Yvan-Charvet, L., Terasaka, N., Pagler, T., Wang, N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 7, 365-375 (2008).
30. Barter, P.J. Hugh Sinclair Lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler. Suppl. 3, 39-47 (2002).
31. Rye, K.A., Barter, P.J. Formation and metabolism of prebeta-migrating, lipid-poor apolipoprotein A-I. Arterioscler. Thromb. Vasc. Biol. 24, 421-428 (2004).
32. Barter, P.J. et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357, 2109-2122 (2007).
33. Schwartz, G.G. et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med. 367, 2089-2099 (2012).
34. Gotto, A.M., Moon, J.E. Safety of inhibition of cholesteryl ester transfer protein with anacetrapib: the DEFINE study. Expert. Rev. Cardiovasc. Ther. 10, 955-963 (2012).
35. Hao, W., Friedman, A. The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model. PLoS One 9, 90497 (2014).
36. Cilla, M., Pena, E., Martinez, M.A. Mathematical modelling of atheroma plaque formation and development in coronary arteries. J. R. Soc. Interface 11, 20130866 (2014).