Metabolism, Excretion, and Pharmacokinetics of [ 14C]-Radiolabeled Aleglitazar: A Phase I, Nonrandomized, Open-Label, Single-Center, Single-Dose Study in Healthy Male Volunteers

Clinical Therapeutics

Volumn 34, Issue 2, 2012, Pages 420-429

  Sturm, Stefan ^a   Seiberling, Michael ^b   Weick, Idelette ^a   Paehler, Axel ^a   Funk, Christoph ^a   Ruf, Thorsten ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b Covance Clinical Research Unit AG ^*  (Switzerland)

Author keywords

Aleglitazar; Excretion; Metabolism; PPAR agonist

Indexed keywords

ALEGLITAZAR;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ADULT; ARTICLE; BODY MASS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG ELIMINATION; DRUG EXCRETION; DRUG FECES LEVEL; DRUG METABOLISM; DRUG TOLERABILITY; DRUG URINE LEVEL; HEADACHE; HERPES VIRUS INFECTION; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; OPEN STUDY; PHARMACODYNAMICS; RADIOACTIVITY; SINGLE DRUG DOSE;

ADULT; AGED; CARBON RADIOISOTOPES; HUMANS; MALE; MIDDLE AGED; OXAZOLES; PPAR ALPHA; PPAR GAMMA; THIOPHENES;

EID: 84856763664     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2011.12.009     Document Type: Article

References (27)

1. van Dieren S., Beulens J.W., van der Schouw Y.T., et al. The global burden of diabetes and its complications: an emerging pandemic. Eur J Cardiovasc Prev Rehabil 2010, 17:S3-S8.
2. Norris S.L., McNally T.K., Zhang X., et al. Published norms underestimate the health-related quality of life among persons with type 2 diabetes. J Clin Epidemiol 2011, 64:358-365.
3. Diabetes Complications Centres for Disease Control and Prevention, Accessed January 5, 2012. http://www.cdc.gov/diabetes/statistics/complications_national.htm.
4. Cefalu W.T. Pharmacotherapy for the treatment of patients with type 2 diabetes mellitus: rationale and specific agents. Clin Pharmacol Ther 2007, 81:636-649.
5. Libby P., Ridker P.M. Inflammation and atherothrombosis: from population biology and bench research to clinical practice. J Am Coll Cardiol 2006, 48:A33-A46.
6. Haffner S.M., Lehto S., Ronnemaa T., et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998, 339:229-234.
7. Vamecq J., Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999, 354:141-148.
8. Lalloyer F., Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2010, 30:894-899.
9. Staels B., Maes M., Zambon A. Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med 2008, 5:542-553.
10. Spiegelman B.M. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998, 47:507-514.
11. Nissen S.E., Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356:2457-2471.
12. FDA Drug Safety Communication: Updated drug labels for pioglitazone-containing medicines US Food and Drug Administration, Accessed September 2011. http://www.fda.gov/Drugs/DrugSafety/ucm266555.htm.
13. Gerstein H.C., Ratner R.E., Cannon C.P., et al. Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation 2010, 121:1176-1187.
14. Mazzone T., Meyer P.M., Feinstein S.B., et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006, 296:2572-2581.
15. Nissen S.E., Nicholls S.J., Wolski K., et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008, 299:1561-1573.
16. Schernthaner G. Pleiotropic effects of thiazolidinediones on traditional and non-traditional atherosclerotic risk factors. Int J Clin Pract 2009, 63:912-929.
17. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004, 351:1106-1118.
18. Henry R.R., Lincoff A.M., Mudaliar S., et al. Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 2009, 374:126-135.
19. Benardeau A., Benz J., Binggeli A., et al. Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. Bioorg Med Chem Lett 2009, 19:2468-2473.
20. Hansen B.C., Tigno X.T., Benardeau A., et al. Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor alpha/gamma agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome. Cardiovasc Diabetol 2011, 10:7.
21. Herz M., Gaspari F., Perico N., et al. Effects of high dose aleglitazar on renal function in patients with type 2 diabetes. Int J Cardiol 2011, 151:136-142.
22. A study with aleglitazar in patients with a recent acute coronary syndrome and type 2 diabetes mellitus ALECARDIO study, Accessed June 2011. http://clinicaltrials.gov/ct2/show/NCT01042769.
23. Sanwald-Ducray P., Liogier D'ardhy X., Jamois C., Banken L. Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: results from a randomized, placebo-controlled clinical study. Clin Pharmacol Ther 2010, 88:197-203.
24. Ericsson H., Hamren B., Bergstrand S., et al. Pharmacokinetics and metabolism of tesaglitazar, a novel dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, after a single oral and intravenous dose in humans. Drug Metab Dispos 2004, 32:923-929.
25. Chang F., Jaber L.A., Berlie H.D., O'Connell M.B. Evolution of peroxisome proliferator-activated receptor agonists. Ann Pharmacother 2007, 41:973-983.
26. Younk L.M., Uhl L., Davis S.N. Pharmacokinetics, efficacy and safety of aleglitazar for the treatment of type 2 diabetes with high cardiovascular risk. Expert Opin Drug Metab Toxicol 2011, 7:753-763.
27. Mogensen C.E. Prevention and treatment of renal disease in insulin-dependent diabetes mellitus. Semin Nephrol 1990, 10:260-273.