Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94–8862) in Individuals With Renal Impairment

Clinical Pharmacology in Drug Development

Volumn 5, Issue 6, 2016, Pages 488-501

  Heinig, Roland ^a   Kimmeskamp Kirschbaum, Nina ^a   Halabi, Atef ^b   Lentini, Silvia ^a  

^a BAYER PHARMA AG   (Germany)

^b CRS Clinical Research Services Kiel GmbH   (Germany)

Author keywords

finerenone (BAY 94 8862); mineralocorticoid receptor antagonist; pharmacokinetics; renal impairment

Indexed keywords

FINERENONE; MINERALOCORTICOID ANTAGONIST; NAPHTHYRIDINE DERIVATIVE;

ADULT; AGED; AREA UNDER THE CURVE; BIOTRANSFORMATION; DIABETIC NEPHROPATHY; FEMALE; HALF LIFE TIME; HUMAN; KIDNEY FAILURE; KIDNEY FUNCTION TEST; MALE; METABOLISM; MIDDLE AGED;

ADULT; AGED; AREA UNDER CURVE; BIOTRANSFORMATION; DIABETIC NEPHROPATHIES; FEMALE; HALF-LIFE; HUMANS; KIDNEY FUNCTION TESTS; MALE; MIDDLE AGED; MINERALOCORTICOID RECEPTOR ANTAGONISTS; NAPHTHYRIDINES; RENAL INSUFFICIENCY;

EID: 84995897394     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1002/cpdd.263     Document Type: Article

References (29)

1. Maron BA, Leopold JA. Aldosterone receptor antagonists: effective but often forgotten. Circulation. 2010;121(7):934–939.
2. Garthwaite SM, McMahon EG. The evolution of aldosterone antagonists. Mol Cell Endocrinol. 2004;217(1-2):27–31.
3. Sechi LA, Novello M, Lapenna R, et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA. 2006;295(22):2638–2645.
4. Metra M, Cotter G, Gheorghiade M, Dei Cas L, Voors AA. The role of the kidney in heart failure. Eur Heart J. 2012;33(17):2135–2142.
5. Sato A, Saruta T. Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy. Am J Hypertens. 2003;16(9 Pt 1):781–788.
6. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–717.
7. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.
8. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–1321.
9. Albert NM, Yancy CW, Liang L, et al. Use of aldosterone antagonists in heart failure. JAMA. 2009;302(15):1658–1665.
10. Delyani JA. Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Kidney Int. 2000;57(4):1408–1411.
11. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69–78.
12. Greenblatt DJ. Adverse reactions to spironolactone. JAMA. 1973;225(1):40.
13. Bärfacker L, Kuhl A, Hillisch A, et al. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7(8):1385–1403.
14. Liu LC, Schutte E, Gansevoort RT, van der Meer P, Voors AA. Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease. Expert Opin Investig Drugs. 2015;24(8):1123–1135.
15. Albrecht-Küpper B, Kretschmer A, Kast R, Baerfacker L, Schaefer S, Kolkhof P. Pronounced cardiac protection by BAY 94-8862, a novel non-steroidal mineralocorticoid receptor antagonist in a preclinical rat model of heart failure. Eur Heart J. 2012;33(Abstract Suppl):7.
16. Delbeck M, Kretschmer A, Kast R, et al. Cardiorenal protection by BAY 94-8862, a novel non-steroidal mineralocorticoid receptor antagonist in a preclinical model of hypertension and diastolic heart failure. Eur Heart J. 2012;33 (Abstract Supplement):772–773 Abstract P4422.
17. Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2453–2463.
18. Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884–894.
19. Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, Wensing G. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone – results from first-in-man and relative bioavailability studies. Fundam Clin Pharmacol. 2016;30(2):172–184.
20. European Medicines Agency. Guideline on the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/2002/WC500162133.pdf. Accessed June 24, 2015.
21. United States Department of Health and Human Services Food and Drug Administration. Guidance for industry pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling. Draft guidance 2010. http://www.fda.gov/downloads/Drugs/Guidances/UCM204959.pdf. Accessed June 24, 2015.
22. European Medicines Agency. Note for guidance on the evaluation of the pharmacokinetics of medicinal products in patients with impaired renal function. 2004. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003123.pdf. Accessed February 21, 2013.
23. US Food and Drug Administration. Guidance for industry. Pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling. 1998;2013(21 February). http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072127.pdf. Accessed June 24, 2015.
24. US Food and Drug Administration. Guidance for Industry: Bioanalytical Method Validation. 2001. http://www.fda.gov/downloads/Drugs/Guidances/ucm070107.pdf. Accessed January 28, 2015.
25. US Food and Drug Administration. Guidance for industry. Pharmacokinetics in patients with impaired renal function — study design, data analysis, and impact on dosing and labeling. 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM204959.pdf. Accessed October 15, 2014.
26. Lalande L, Charpiat B, Leboucher G, Tod M. Consequences of renal failure on non-renal clearance of drugs. Clin Pharmacokinet. 2014;53(6):521–532.
27. Dreisbach AW, Lertora JJ. The effect of chronic renal failure on hepatic drug metabolism and drug disposition. Semin Dial. 2003;16(1):45–50.
28. Touchette MA, Slaughter RL. The effect of renal failure on hepatic drug clearance. Drug Intell Clin Pharm. 1991;25(11):1214–1224.
29. Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone versus eplerenone in patients with worsening chronic heart failure and diabetes and/or chronic kidney disease. Eur Heart J. In press.