title: Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone - results from first-in-man and relative bioavailability studies.
abstract: The safety, tolerability and pharmacokinetics of the selective nonsteroidal mineralocorticoid receptor antagonist finerenone were evaluated in healthy male volunteers in two randomized, single-centre studies. Study 1 was a first-in-man, single-blinded, placebo-controlled, parallel-group, dose-escalation study. Fasted participants (n = 45) received single oral doses of finerenone 1-40 mg polyethylene glycol (PEG) solution or placebo. Study 2 was a relative bioavailability study comparing a finerenone 10 mg immediate-release (IR) tablet with finerenone 10 mg PEG solution in the fasted state, investigating the effect of a high-fat/high-calorie meal on the pharmacokinetics of the IR tablet and assessing a further dose escalation to finerenone 80 mg (eight × finerenone 10 mg IR tablets), in an open-label, fourfold crossover design (n = 15). Finerenone was rapidly absorbed from PEG solution (median time to maximum plasma concentration [tmax ]: 0.500-1.00 h), exhibited dose-linear pharmacokinetics and was rapidly eliminated from plasma (geometric mean terminal half-life [t½ ]: 1.70-2.83 h). Finerenone IR tablets demonstrated similar pharmacokinetics (median tmax : 0.750-2.50 h; geometric mean t½ : 1.89-4.29 h) with, however, enhanced bioavailability versus PEG solution (least-squares mean tablet/solution ratio of 187% for area under the plasma-concentration curve [AUC] and maximum plasma concentration [Cmax ]). High-fat/high-calorie food affected the rate but not the extent of finerenone absorption. Finerenone was well tolerated and did not influence clinical laboratory parameters, blood pressure, heart rate, urinary electrolytes or neurohormones, including serum aldosterone and angiotensin II. In conclusion, finerenone has favourable pharmacokinetics and tolerability in healthy men, and is suitable for dosing independent of food intake.
authors.affiliation: Clinical Sciences, Clinical Pharmacology, Cardiovascular and Hematology, Bayer Pharma AG, Pharma Research Centre, 42096, Wuppertal, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lentini
authors.affiliation: Clinical Sciences, Clinical Pharmacology, Cardiovascular and Hematology, Bayer Pharma AG, Pharma Research Centre, 42096, Wuppertal, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Heinig
authors.affiliation: Global Research & Development Statistics, Bayer Pharma AG, Pharma Research Centre, 42096, Wuppertal, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Kimmeskamp-Kirschbaum
authors.affiliation: Clinical Sciences, Clinical Pharmacology, Cardiovascular and Hematology, Bayer Pharma AG, Pharma Research Centre, 42096, Wuppertal, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Wensing
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004435:Eating / Q000502:physiology; D005215:Fasting; D018565:Food-Drug Interactions / Q000502:physiology; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009287:Naphthyridines / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019999:Pharmaceutical Solutions / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D013607:Tablets / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D009287:Naphthyridines; D019999:Pharmaceutical Solutions; D013607:Tablets; C576501:finerenone
keywords: finerenone; mineralocorticoid receptor antagonist; pharmacokinetics; safety; tolerability