Biotransformation of Finerenone, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, in Dogs, Rats, and Humans, In Vivo and In Vitro.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Michael GerischThomas Schwarz

Abstract

Mass balance and biotransformation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, were investigated in four healthy male volunteers following a single oral administration of 10 mg (78 μCi) of [14C]finerenone and compared with data from studies in dogs and rats. The total recovery of the administered radioactivity was 101% in humans, 94.7% in dogs, and 95.2% in rats. In humans, radioactivity was mainly excreted renally (80%); in rats, it was primarily the biliary/fecal route (76%); and in dogs, excretion was more balanced. Finerenone was extensively metabolized in all species by oxidative biotransformation, with minor amounts of unchanged drug in excreta (humans: 1%; dogs, rats: <9%). In vitro studies suggested cytochrome P450 3A4 was the predominant enzyme involved in finerenone metabolism in humans. Primary metabolic transformation involved aromatization of the dihydronaphthyridine moiety of metabolite M1 as a major clearance pathway with a second oxidative pathway leading to M4. These were both prone to further oxidative biotransformation reactions. Naphthyridine metabolites (M1-M3) were the dominant metabolites identified in human plasma, with no on-target pharmacological activity. In dog plasma, finere...Continue Reading

References

Nov 14, 1997·Biochemical Pharmacology·A KernK F Sewing
Jul 2, 1998·Journal of Pharmaceutical Sciences·C E HopG Kwei
Aug 26, 1998·Drug Metabolism Reviews·C A Mugford, G L Kedderis
Jul 24, 2010·The Journal of Biological Chemistry·Jérôme FagartPeter Kolkhof
Mar 2, 2011·ChemMedChem·Steven R LaPlanteOliver Hucke
Feb 24, 2015·Advances in Chronic Kidney Disease·Michael H SchwenkAndrew S Bomback
Jun 18, 2015·Current Opinion in Nephrology and Hypertension·Peter KolkhofFrank Eitner
Sep 2, 2015·JAMA : the Journal of the American Medical Association·George L BakrisUNKNOWN Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group

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Citations

Mar 4, 2020·European Journal of Drug Metabolism and Pharmacokinetics·Roland HeinigStephanie Loewen
Sep 6, 2020·Angewandte Chemie·Andreas LerchenVarinder K Aggarwal
Oct 26, 2020·European Heart Journal·Rajiv AgarwalFaiez Zannad
Apr 8, 2021·Journal of the American Chemical Society·Minghao FengDavide Audisio
Jun 1, 2021·Journal of Cardiovascular Pharmacology·Kristin WatsonChristine E Shulenberger
May 30, 2021·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Stavroula Veneti, Konstantinos Tziomalos
Aug 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Peter KolkhofUlrich Kintscher
Sep 15, 2021·Drugs·James E Frampton
Nov 17, 2021·CPT: Pharmacometrics & Systems Pharmacology·Thomas WendlThomas Eissing
Nov 24, 2021·British Journal of Pharmacology·Ulrich KintscherPeter Kolkhof

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