The selective mineralocorticoid receptor modulator AZD9977 reveals differences in mineralocorticoid effects of aldosterone and fludrocortisone

Journal of the Renin-angiotensin-aldosterone System : JRAAS
Krister BambergJudith Hartleib-Geschwindner

Abstract

AZD9977 is a novel mineralocorticoid receptor (MR) modulator, which in preclinical studies demonstrated organ protection without affecting aldosterone-regulated urinary electrolyte excretion. However, when tested in humans, using fludrocortisone as an MR agonist, AZD9977 exhibited similar effects on urinary Na+/K+ ratio as eplerenone. The aim of this study is to understand whether the contradictory results seen in rats and humans are due to the mineralocorticoid used. Rats were treated with single doses of AZD9977 or eplerenone in combination with either aldosterone or fludrocortisone. Urine was collected for five to six hours and total amounts excreted Na+ and K+ were assessed. AZD9977 dose-dependently increased urinary Na+/K+ ratio in rats when tested against fludrocortisone, but not when tested against aldosterone. Eplerenone dose-dependently increased urinary Na+/K+ ratio when tested against fludrocortisone as well as aldosterone. The data suggest that the contrasting effects of AZD9977 on urinary electrolyte excretion observed in rats and humans are due to the use of the synthetic mineralocorticoid fludrocortisone. Future clinical studies are required to confirm the reduced electrolyte effects of AZD9977 and the subsequent...Continue Reading

References

Oct 1, 1975·Clinical Pharmacology and Therapeutics·L RamsayM Tidd
Apr 2, 2003·The New England Journal of Medicine·Bertram PittUNKNOWN Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators
May 27, 1955·Annals of the New York Academy of Sciences·G W THORNA E RENOLD
Aug 6, 2004·The New England Journal of Medicine·Biff F Palmer
Feb 29, 2008·Journal of Pharmacological and Toxicological Methods·Philip E BrandishJames C Hershey
Nov 16, 2010·The New England Journal of Medicine·Faiez ZannadUNKNOWN EMPHASIS-HF Study Group
Mar 18, 2011·Kidney International·Jean-Philippe BertocchioFrederic Jaisser
Feb 19, 2015·Pharmacology Research & Perspectives·Michael J Curtis, Darrell R Abernethy
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
Oct 16, 2015·Journal of Cardiovascular Pharmacology·Elise Gomez-Sanchez
Apr 2, 2016·Journal of the American Heart Association·Sandesh DevSarah J Tracy

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Citations

Nov 13, 2020·Drug Development Research·Vishal PatelMukul Jain
Aug 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Peter KolkhofUlrich Kintscher
Oct 27, 2021·British Journal of Pharmacology·Dorien ClarisseAchim Lother

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