دورية أكاديمية
أعرض في EDS

Dose-Exposure-Response Analysis of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone on UACR and eGFR: An Analysis from FIDELIO-DKD.

التفاصيل البيبلوغرافية
العنوان: Dose-Exposure-Response Analysis of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone on UACR and eGFR: An Analysis from FIDELIO-DKD.
المؤلفون: Goulooze SC; Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands., Heerspink HJL; Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Noort M; Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands., Snelder N; Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands., Brinker M; Bayer AG, Pharmaceuticals R&D, Clinical Development, Leverkusen, Germany., Lippert J; Bayer AG, Pharmaceuticals R&D, Pharmacometrics, Building B106, Room 205, 51368, Leverkusen, Germany., Eissing T; Bayer AG, Pharmaceuticals R&D, Pharmacometrics, Building B106, Room 205, 51368, Leverkusen, Germany. thomas.eissing@bayer.com.
المصدر: Clinical pharmacokinetics [Clin Pharmacokinet] 2022 Jul; Vol. 61 (7), pp. 1013-1025. Date of Electronic Publication: 2022 May 05.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Country of Publication: Switzerland NLM ID: 7606849 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1926 (Electronic) Linking ISSN: 03125963 NLM ISO Abbreviation: Clin Pharmacokinet Subsets: MEDLINE
أسماء مطبوعة: Publication: [Switzerland] : Adis, part of Springer Science+Business Media
Original Publication: New York, ADIS Press.
مواضيع طبية MeSH: Diabetes Mellitus, Type 2*/complications , Diabetes Mellitus, Type 2*/drug therapy , Renal Insufficiency*/complications , Renal Insufficiency, Chronic*/drug therapy , Sodium-Glucose Transporter 2 Inhibitors*, Glomerular Filtration Rate ; Humans ; Mineralocorticoid Receptor Antagonists/pharmacology ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Naphthyridines
مستخلص: Background and Objective: Finerenone reduces the risk of kidney failure in patients with chronic kidney disease and type 2 diabetes. Changes in the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are surrogates for kidney failure. We performed dose-exposure-response analyses to determine the effects of finerenone on these surrogates in the presence and absence of sodium glucose co-transporter-2 inhibitors (SGLT2is) using individual patient data from the FIDELIO-DKD study.
Methods: Non-linear mixed-effects population pharmacokinetic/pharmacodynamic models were used to quantify disease progression in terms of UACR and eGFR during standard of care and pharmacodynamic effects of finerenone in the presence and absence of SGLT2i use.
Results: The population pharmacokinetic/pharmacodynamic models adequately described effects of finerenone exposure in reducing UACR and slowing eGFR decline over time. The reduction in UACR achieved with finerenone during the first year predicted its subsequent effect in slowing progressive eGFR decline. SGLT2i use did not modify the effects of finerenone. The population pharmacokinetic/pharmacodynamic model demonstrated with 97.5% confidence that finerenone was at least 94.1% as efficacious in reducing UACR in patients using an SGLT2i compared with patients not using an SGLT2i based on the 95% confidence interval of the SGLT2i-finerenone interaction from 94.1 to 122%. The 95% confidence interval of the SGLT2i-finerenone interaction for the UACR-mediated effect on chronic eGFR decline was 9.5-144%.
Conclusions: We developed a model that accurately describes the finerenone dose-exposure-response relationship for UACR and eGFR. The model demonstrated that the early UACR effect of finerenone predicted its long-term effect on eGFR decline. These effects were independent of concomitant SGLT2i use.
(© 2022. The Author(s).)
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المشرفين على المادة: 0 (Mineralocorticoid Receptor Antagonists)
0 (Naphthyridines)
0 (Sodium-Glucose Transporter 2 Inhibitors)
0 (finerenone)
تواريخ الأحداث: Date Created: 20220504 Date Completed: 20220719 Latest Revision: 20240624
رمز التحديث: 20240624
مُعرف محوري في PubMed: PMC9287422
DOI: 10.1007/s40262-022-01124-3
PMID: 35508594
قاعدة البيانات: MEDLINE
الوصف
تدمد:1179-1926
DOI:10.1007/s40262-022-01124-3