Esaxerenone is a novel non-steroidal
mineralocorticoid receptor antagonisit (MR blocker), whose unique binding to the MR-
ligand domain yields a stronger MR antagonistic effect and higher selectivity than existing MR antagonisits.
Esaxerenone was approved for the treatment of
hypertension in Japan in January 2019.
Esaxerenone suppresses the reduction of urinary Na+/K+ ratio in adrenalectomized rats and blood pressure increase,
proteinuria, and renal tissue lesions in
salt-sensitive hypertensive rats-all in a dose-dependent manner.
Esaxerenone is rapidly absorbed and reaches intracellular targets because of its high membrane permeability, exhibits high bioavailability with small interindividual exposure variation, and is metabolized via several pathways (e.g., oxidation, glucuronidation, and hydrolysis), which is associated with low
drug-drug interaction risk. As
esaxerenone is slightly excreted into urine, its exposure is similar between elderly and non-elderly patients, and between patients with normal and moderately deteriorated renal function. Given its 19-hour half-life, once-daily administration would have a sustainable
antihypertensive effect. The ESAX-HTN phase 3 study demonstrated the non-inferiority of
esaxerenone's
antihypertensive effect versus that of
eplerenone in
essential hypertension. Another study showed a stable
antihypertensive effect for 52 weeks as monotherapy or combination
therapy. In hypertensive patients with moderate impairment or both
type 2 diabetes and
albuminuria treated with a renin-angiotensin system inhibitor,
esaxerenone elicited a stable
antihypertensive effect and manageable
hyperkalemia incidence with titration from a low dose and monitoring including serum
potassium. Thus, with careful monitoring of serum
potassium,
esaxerenone can be administered to patients with moderate renal impairment or both diabetes and
albuminuria.