Table 1.

The Pharmacokinetics of MRAs.

Agent	Spironolactone	Eplerenone	Finerenone	Esaxerenone	Apararenone	Ocedurenone	Miricorilant	Balcinrenone	Drospirenone/Estetrol	Canrenone
Name	SC 9420		BAY 94-8862	CS-3150	MT-3995	KBP-5074	CORT-118335	AZD-9977		SC 9376
Dose	10mg/20mg	25mg/50mg	10mg/20mg	1.25mg/2.5mg/5mg	2.5mg/5mg/10mg	0.25mg/0.5mg	in development	in development
Company	Pfizer	Pfizer	Bayer	Daiichi-Sankyo Company Limited, Japan	Mitsubishi Tanabe Pharma Corporation	KBP Biosciences	Corcept, Argenta Discovery	AstraZeneca	Mithra Pharmaceuticals, Estetra S.A., Libbs
Generation of MRA	first	second	third	third	MRA	MRA	GRA; MRA	MR regulator	MRA; PR agonist; ARA; selective ER regulator	first
Steroidal/Nonsteroidal	steroidal	steroidal	nonsteroidal	nonsteroidal	nonsteroidal	nonsteroidal	nonsteroidal	nonsteroidal		steroidal
Molecular Formular	C24H32O4S	C24H3O6	C21H22N4O3	C22H21F3N2O4S	C17H17FN2O4S	C28H30ClN5O2	C24H23F3N2O2	C20H18FN3O5	C24H30O3	C22H28O3
Structure
Characteristic	potent and unselective	less potent and more selective than spironolactone	more potent and more selective than spironolactone	more potent and more selective than eplerenone	more potent and more selective than spironolactone		more potent and more selective; moderate affinity to MR	no affinity to GR/PR/AR
Heart-kidney distribution ratio	1:6	1:3	1:1; cannot across the Blood-Brain Barrier	1:1
t½	13~24h(qd/bid); 9~16hqid	4-6h	1.7-2.8h	20-30h	275-285h for parent drug;>1000h for active metabolite			increased with dose	31h
Tmax	2.6-3.05h	1.5h	0.75-1h	1.5-4h	4h			0.5-0.8h	1-2h
Cmax	209-301ng/ml	–	160ug/L(20mg)						37ng/ml
MR IC50	24	990	17.8				moderate affinity to MR
AR IC50	77	≥21240	≥10000					almost no affinity to GR/PR/AR	almost no affinity to GR/AR
GR IC50	2410	≥21980	≥10000
PR IC50	740	≥31210	≥10000
Oral bioavailability	>90%	69%	86.50%						76-85%
Protein binding ratio	>90%	33%-60%	92%						95-97%
Metabolism	prodrug with multiple active metabolites	no active metabolites	no active metabolites	n/a	metabolite with low activity (MR binding affinity one-fiftieth of that of apararenone)			n/a		the active metabolites of spironolactone
Hyperkalemia	high risk	high risk	low risk	low risk					no risk
Excretion	<1% unchanged drug recovered in urine; 10-15% of dose excreted in urine form of metabolites	66% of dose excreted via urine; <3% unchanged drug recovered from urine	80% of dose excreted via urine; <1% unchanged drug excreted in urine	38.5% of dose excreted in urine; <2% unchanged drug excreted in urine	<14% of dose excreted in urine			24–37% of dose excreted in urine; 20% of dose excreted unchanged in urine
Sex-like ADR	common	less than spironolactone	no statistics difference with placebo group
Dose adjust based on renal function	excretion through the kidney	cannot be removed by hemodialysis	decrease dose in patients with eGFR≤60 and prohibit when eGFR<25						decrease dose in patients with eGFR 30-50
Indication	PA; HBP; hypokalemia; edema; HF	congestive heart failure; HBP	T2DM with CKD, ESRD, CVD, congestive heart failure	HBP, DKD(clinical trial phase)	DKD	HBP, DKD, HN	obesity; prostate cancer; metabolism disorder	DKD	contraception	HBP
Contraindication	not recommended to CRF	not recommended to CRF

The unit of IC50 is nmol/L. the unit of eGFR is ml/min/1.73m². PR, progesterone receptor. ER, estrogen receptor. AR, androgen receptor. MRA, mineralocorticoid receptor antagonist. t½, geometric mean terminal half-life. Tmax, median time to maximum plasma concentration. Cmax, maximum plasma concentration. ADR, adverse drug reactions. eGFR, estimated glomerular filtration rate. PA, primary aldosteronism. HBP, hypertension. CKD, chronic kidney diseases. DKD, diabetic kidney diseases. HN, hypertensive nephropathy. ESRD, end-stage renal disease.