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.

European Journal of Drug Metabolism and Pharmacokinetics
Roland HeinigStephanie Loewen

Abstract

Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist. In vivo and in vitro studies were performed to assess absolute bioavailability of finerenone, the effect of metabolic enzyme inhibitors on the pharmacokinetics of finerenone and its metabolites, the quantitative contribution of the involved enzymes cytochrome P450 (CYP) 3A4 and CYP2C8 and the relevance of gut wall versus liver metabolism. The pharmacokinetics, safety and tolerability of finerenone (1.25-10 mg orally or 0.25-1.0 mg intravenously) were evaluated in healthy male volunteers in four crossover studies. Absolute bioavailability was assessed in volunteers receiving finerenone orally and by intravenous infusion (n = 15) and the effects of erythromycin (n = 15), verapamil (n = 13) and gemfibrozil (n = 16) on finerenone pharmacokinetics were investigated. Finerenone was also incubated with cryopreserved human hepatocytes in vitro in the presence of erythromycin, verapamil or gemfibrozil. Finerenone absolute bioavailability was 43.5% due to first-pass metabolism in the gut wall and liver. The geometric mean AUC0-∞ ratios of finerenone (drug + inhibitor/drug alone) were 3.48, 2.70 and 1.10 with erythromycin, verapamil and gemfibrozil, respective...Continue Reading

References

Nov 1, 1987·British Journal of Clinical Pharmacology·K K HlaA N Latham
Dec 17, 2004·Journal of Clinical Pharmacology·Robert L WalskyR Scott Obach
Feb 10, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mary F PaineDarryl C Zeldin
Jun 23, 2007·Journal of Clinical Pharmacology·Toshiaki OkudairaKyoichi Ohashi
Apr 7, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael GertzAleksandra Galetin
Mar 4, 2011·Clinical Pharmacology and Therapeutics·J HonkalammiJ T Backman
Jul 21, 2011·Molecular and Cellular Endocrinology·Peter Kolkhof, Steffen A Borden
Mar 16, 2012·Clinical Pharmacology and Therapeutics·J S FloydB M Psaty
Apr 5, 2012·Clinical Pharmacology and Therapeutics·J HonkalammiJ T Backman
Mar 14, 2014·Journal of Cardiovascular Pharmacology·Peter KolkhofStefan Schäfer
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
Sep 2, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael GerischThomas Schwarz

❮ Previous
Next ❯

Citations

Sep 2, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael GerischThomas Schwarz
Mar 4, 2020·European Journal of Drug Metabolism and Pharmacokinetics·Roland HeinigStephanie Loewen
Jun 1, 2021·Journal of Cardiovascular Pharmacology·Kristin WatsonChristine E Shulenberger
Sep 15, 2021·Drugs·James E Frampton
Nov 17, 2021·CPT: Pharmacometrics & Systems Pharmacology·Thomas WendlThomas Eissing
Oct 27, 2021·British Journal of Pharmacology·Dorien ClarisseAchim Lother

❮ Previous
Next ❯

Software Mentioned

WinNonlin

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.