{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T21:21:15Z","timestamp":1768684875330,"version":"3.49.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1007\/s13318-020-00610-y","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T15:02:52Z","timestamp":1583247772000},"page":"433-444","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Results from Drug\u2013Drug Interaction Studies In Vitro and In Vivo Investigating the Effect of Finerenone on the Pharmacokinetics of Comedications"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-5428","authenticated-orcid":false,"given":"Roland","family":"Heinig","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Gerisch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Bairlein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Nagelschmitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Loewen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"610_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1161\/HYPERTENSIONAHA.114.04488","volume":"65","author":"J Bauersachs","year":"2015","unstructured":"Bauersachs J, Jaisser F, Toto R. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015;65:257\u201363.","journal-title":"Hypertension"},{"key":"610_CR2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1053\/j.ackd.2014.08.003","volume":"22","author":"MH Schwenk","year":"2015","unstructured":"Schwenk MH, Hirsch JS, Bomback AS. Aldosterone blockade in CKD: emphasis on pharmacology. Adv Chronic Kidney Dis. 2015;22:123\u201332.","journal-title":"Adv Chronic Kidney Dis"},{"key":"610_CR3","doi-asserted-by":"publisher","first-page":"T125","DOI":"10.1530\/JOE-16-0600","volume":"234","author":"P Kolkhof","year":"2017","unstructured":"Kolkhof P, B\u00e4rfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234:T125\u2013T140140.","journal-title":"J Endocrinol"},{"key":"610_CR4","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/164_2016_76","volume":"243","author":"P Kolkhof","year":"2017","unstructured":"Kolkhof P, Jaisser F, Kim SY, Filippatos G, Nowack C, Pitt B. Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: comparison at bench and bedside. Handb Exp Pharmacol. 2017;243:271\u2013305.","journal-title":"Handb Exp Pharmacol"},{"key":"610_CR5","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1002\/cmdc.201200081","volume":"7","author":"L B\u00e4rfacker","year":"2012","unstructured":"B\u00e4rfacker L, Kuhl A, Hillisch A, Grosser R, Figueroa-Perez S, Heckroth H, Nitsche A, Erguden JK, Gielen-Haertwig H, Schlemmer KH, Mittendorf J, Paulsen H, Platzek J, Kolkhof P. Discovery of BAY 94\u20138862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7:1385\u2013403.","journal-title":"ChemMedChem"},{"key":"610_CR6","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1097\/MNH.0000000000000147","volume":"24","author":"P Kolkhof","year":"2015","unstructured":"Kolkhof P, Nowack C, Eitner F. Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015;24:417\u201324.","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"610_CR7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/FJC.0000000000000091","volume":"64","author":"P Kolkhof","year":"2014","unstructured":"Kolkhof P, Delbeck M, Kretschmer A, Steinke W, Hartmann E, Barfacker L, Eitner F, Albrecht-Kupper B, Schafer S. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64:69\u201378.","journal-title":"J Cardiovasc Pharmacol"},{"key":"610_CR8","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.mce.2011.06.025","volume":"350","author":"P Kolkhof","year":"2012","unstructured":"Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol Cell Endocrinol. 2012;350:310\u20137.","journal-title":"Mol Cell Endocrinol"},{"key":"610_CR9","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1001\/jama.2015.10081","volume":"314","author":"GL Bakris","year":"2015","unstructured":"Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314:884\u201394.","journal-title":"JAMA"},{"key":"610_CR10","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1093\/eurheartj\/ehw132","volume":"37","author":"G Filippatos","year":"2016","unstructured":"Filippatos G, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, Maggioni AP, Ponikowski P, Voors AA, Zannad F, Kim SY, Nowack C, Palombo G, Kolkhof P, Kimmeskamp-Kirschbaum N, Pieper A, Pitt B. A randomized controlled study of finerenone vs eplerenone in patients with worsening chronic heart failure and diabetes mellitus and\/or chronic kidney disease. Eur Heart J. 2016;37:2105\u201314.","journal-title":"Eur Heart J"},{"key":"610_CR11","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1093\/eurheartj\/eht187","volume":"34","author":"B Pitt","year":"2013","unstructured":"Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, Kolkhof P, Kim SY, Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94\u20138862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34:2453\u201363.","journal-title":"Eur Heart J"},{"key":"610_CR12","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1111\/fcp.12170","volume":"30","author":"S Lentini","year":"2016","unstructured":"Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, Wensing G. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone\u2014results from first-in-man and relative bioavailability studies. Fundam Clin Pharmacol. 2016;30:172\u201384.","journal-title":"Fundam Clin Pharmacol"},{"key":"610_CR13","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s13318-018-0483-9","volume":"43","author":"R Heinig","year":"2018","unstructured":"Heinig R, Gerisch M, Engelen A, Nagelschmitz J, Loewen S. Pharmacokinetics of the novel, selective, non-steroidal mineralocorticoid receptor antagonist finerenone in healthy volunteers: results from an absolute bioavailability study and drug-drug interaction studies in vitro and in vivo. Eur J Drug Metab Pharmacokinet. 2018;43:715\u201327.","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"610_CR14","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1124\/dmd.118.083337","volume":"46","author":"M Gerisch","year":"2018","unstructured":"Gerisch M, Heinig R, Engelen A, Lang D, Kolkhof P, Radtke M, Platzek J, Lovis K, Rohde G, Schwarz T. Biotransformation of finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, in dogs, rats, and humans, in vivo and in vitro. Drug Metab Dispos. 2018;46:1546\u201355.","journal-title":"Drug Metab Dispos"},{"key":"610_CR15","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1002\/cpdd.263","volume":"5","author":"R Heinig","year":"2016","unstructured":"Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, Lentini S. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94\u20138862) in individuals with renal impairment. Clin Pharmacol Drug Dev. 2016;5:488\u2013501.","journal-title":"Clin Pharmacol Drug Dev"},{"key":"610_CR16","unstructured":"European Medicines Agency (2012). Guideline on the investigation of drug interactions. 2012. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-investigation-drug-interactions_en.pdf. Accessed 26 Oct 2019."},{"key":"610_CR17","unstructured":"US Food and Drug Administration (2017) Clinical drug interaction studies\u2014study design, data analysis, and clinical implications guidance for industry. 2017. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/clinical-drug-interaction-studies-study-design-data-analysis-and-clinical-implications-guidance. Accessed 26 Oct 2019."},{"key":"610_CR18","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/BF03258417","volume":"4","author":"L Duursema","year":"1992","unstructured":"Duursema L, M\u00fcller FO, Hundt HKL, Heyns ADP, Meyer BH, Luus HG. Model to detect warfarin-drug interactions in man. Drug Invest. 1992;4:395\u2013402.","journal-title":"Drug Invest."},{"key":"610_CR19","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1517\/17425255.2012.685237","volume":"8","author":"YM Wang","year":"2012","unstructured":"Wang YM, Ong SS, Chai SC, Chen T. Role of CAR and PXR in xenobiotic sensing and metabolism. Expert Opin Drug Metab Toxicol. 2012;8:803\u201317.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"610_CR20","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/clpt.1987.168","volume":"42","author":"LD Heimark","year":"1987","unstructured":"Heimark LD, Gibaldi M, Trager WF, O'Reilly RA, Goulart DA. The mechanism of the warfarin-rifampin drug interaction in humans. Clin Pharmacol Ther. 1987;42:388\u201394.","journal-title":"Clin Pharmacol Ther"},{"key":"610_CR21","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1177\/0091270003262950","volume":"44","author":"CR Shadle","year":"2004","unstructured":"Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA. Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol. 2004;44:215\u201323.","journal-title":"J Clin Pharmacol"},{"key":"610_CR22","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1177\/00912709922008380","volume":"39","author":"C Weber","year":"1999","unstructured":"Weber C, Banken L, Birnboeck H, Schulz R. Effect of the endothelin-receptor antagonist bosentan on the pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol. 1999;39:847\u201354.","journal-title":"J Clin Pharmacol"},{"key":"610_CR23","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/clpt.2013.187","volume":"95","author":"ML Vieira","year":"2014","unstructured":"Vieira ML, Kirby B, Ragueneau-Majlessi I, Galetin A, Chien JY, Einolf HJ, Fahmi OA, Fischer V, Fretland A, Grime K, Hall SD, Higgs R, Plowchalk D, Riley R, Seibert E, Skordos K, Snoeys J, Venkatakrishnan K, Waterhouse T, Obach RS, Berglund EG, Zhang L, Zhao P, Reynolds KS, Huang SM. Evaluation of various static in vitro-in vivo extrapolation models for risk assessment of the CYP3A inhibition potential of an investigational drug. Clin Pharmacol Ther. 2014;95:189\u201398.","journal-title":"Clin Pharmacol Ther"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00610-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s13318-020-00610-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-020-00610-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:57:52Z","timestamp":1614733072000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s13318-020-00610-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,3]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["610"],"URL":"https:\/\/doi.org\/10.1007\/s13318-020-00610-y","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"value":"0378-7966","type":"print"},{"value":"2107-0180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,3]]},"assertion":[{"value":"3 March 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The studies presented in this manuscript were funded by Bayer AG.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"RH, MG, MB and JN are employees of Bayer AG. SL is an employee of Chrestos Concept GmbH & Co. KG, which received funding for this analysis from Bayer AG. In addition, RH, MG and JN have stock in Bayer AG, but are not paid in stock or stock options.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study before study commencement.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}