Delving into the Latest Updates on Canrenone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Canrenone (USAN), canrenone

+ [2]

Target

MR

Mechanism

MR modulators(Mineralocorticoid receptor modulators)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Hypertension

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H28O3

InChIKeyUJVLDDZCTMKXJK-WNHSNXHDSA-N

CAS Registry976-71-6

Author: Milaras, Nikias ; Pagkalidou, Eirini ; Zarifis, Ippokratis ; Sagris, Marios ; Theofilis, Panagiotis ; Bougioukas, Konstantinos I. ; Fragakis, Nikolaos ; Samaras, Athanasios ; Karakasis, Paschalis ; Tousoulis, Dimitris ; Pamporis, Konstantinos ; Bougioukas, Konstantinos I ; Giannakoulas, George ; Xanthos, Theodoros

INTRODUCTIONSeveral randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF.MATERIALS AND METHODSMEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE).RESULTSTotally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]).CONCLUSIONSMRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.

10 Jun 2024·Biomedical Papers

Novel approach to adherence assessment based on parent drug and metabolite pharmacokinetics: pilot study with spironolactone

Article

Author: Maresova, Vera ; Hartinger, Jan Miroslav ; Pilkova, Alena ; Slanar, Ondrej ; Nikrynova Nguyen, Thi Minh Phuong ; Widimsky, Jiri ; Kurcova, Ivana ; Sima, Martin

AIMThe aim of this study was to evaluate adherence to spironolactone in a group of unselected patients with arterial hypertension by analysis of measured serum spironolactone and canrenone concentrations according to a proposed two-step decision scheme based on pharmacokinetic considerations.MATERIALS AND METHODSSimulation of serum concentration-time profiles of spironolactone and canrenone based on population pharmacokinetic parameters described in literature and a body weight-normalized spironolactone dose / canrenone level nomogram derived from a group of adherent patients with conservatively treated primary hyperaldosteronism, were used to create a two-step decision scheme. 71 outpatients treated with spironolactone for resistant hypertension with spironolactone and canrenone serum concentrations measured between 2018 and 2021 were analyzed according to the proposed scheme. We compared our proposed methodology to the standard approach for adherence testing.RESULTSWith the most sensitive traditional approach to adherence assessment through detectable serum concentrations of spironolactone and/or canrenone, 9 (12.7%) non-adherent patients were identified. With our two-step assessment of adherence, we were able to identify 18 (25.4%) non-adherent patients.CONCLUSIONConsideration of the pharmacokinetic properties of parental drug and its metabolite led to improved sensitivity in non-adherence detection in patients with arterial hypertension. This approach enables better interpretation of measured spironolactone and canrenone serum concentrations and should be used in clinical practice.

01 Apr 2024·Clinical Biochemistry

Spironolactone metabolite causes falsely increased progesterone in the Abbott Architect immunoassay

Article

Author: Wiencek, Joesph R ; Bazydlo, Lindsay A L ; McCartney, Christopher R ; Hee Kim, Su ; Sarpong, Kwabena A N

BACKGROUNDImmunoassays are important for routine clinical testing and medical diagnosis. However, they are limited by cross-reactivity especially at low analyte concentrations. There is a critical need to investigate compounds that can interfere with immunoassays. Herein, we describe the identification of canrenone, a spironolactone metabolite that falsely increases progesterone concentrations on the Abbott Architect i2000 Immunoassay.METHODSSerum samples and assay diluents were spiked with spironolactone or canrenone and progesterone concentrations were measured on the Architect i2000 and Immulite XPi immunoassay platforms. Blood samples from patients taking spironolactone were analyzed with liquid chromatography-tandem mass spectrometry to evaluate the intrinsic response of progesterone concentrations to the presence of canrenone.RESULTSWe measured approximately 10-fold higher progesterone concentrations on the Abbott Architect i2000 compared to reference immunoassay analyzers (Siemens Immulite XPi and Roche Cobas e601/602), suggesting an analytical error which is unique to the Architect i2000 antibody and/or assay conditions. By measuring serum progesterone after addition of spironolactone or canrenone to serum samples, we found that canrenone falsely increased progesterone on the Architect i2000 immunoassay. However, this interference was more pronounced at low serum progesterone concentrations. Moreover, a strong positive correlation was seen between canrenone and measured serum progesterone concentrations.CONCLUSIONSOur investigations are important for individuals who require progesterone measurements using the Architect i2000 immunoassay, especially because it is unlikely for clinicians to order canrenone measurements alongside progesterone measurements for individuals taking spironolactone. Further research is needed to determine whether canrenone can influence progesterone measurements on other immunoassay systems.

100 Deals associated with Canrenone

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External Link

KEGG	Wiki	ATC	Drug Bank
D03363	Canrenone	C03DA03	DB12221

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Hypertension	-	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


[PP.09.18] (ESH2017)	Not Applicable	Essential Hypertension	-	Canrenone 50 mg/day	bjktnufeth(zdcpzcnhlo) = fnduwqetkc tamzcooztb (uhuxvfrtsr )	Positive	01 Sep 2017
				Canrenone 100 mg/day	bjktnufeth(zdcpzcnhlo) = wabtxhsekb tamzcooztb (uhuxvfrtsr )
NCT02687178 (ESCAPE-IT, Pubmed \| Cardiovasc Ther)	Phase 4	Hypertension Add-on	175	Canrenone 50 mg	xfmjmeuaho(xzrjnswzsy) = txfybalcef lljgryqutc (mowuumjpgl ) View more	-	01 Feb 2017
				Canrenone 100 mg	xfmjmeuaho(xzrjnswzsy) = zatvoduyog lljgryqutc (mowuumjpgl ) View more
PP.LB02.07 (ESH2015)	Not Applicable	plasma aldosterone levels \| aldosterone \| sodium influx ... View more	315	ARBs + Canrenone	qeansmbnky(vbcvsteorv) = odpdhczmhf newzuqvklj (mlbmqjbujl ) View more	Positive	01 Jun 2015
				ARBs + Hydrochlorothiazide	qeansmbnky(vbcvsteorv) = zruarkrmpo newzuqvklj (mlbmqjbujl ) View more
NCT00403910 (AREA IN-CHF, Pubmed \| Eur J Heart Fail)	Phase 3	Chronic heart failure	-	Canrenone	(otjoeatlli) = jmviwsqmvi kbyrasllgc (fkefoxvkvh ) View more	-	01 Jan 2009
				Placebo	(otjoeatlli) = bjrgmdltrn kbyrasllgc (fkefoxvkvh ) View more
NCT00403910 (AREA IN-CHF, Pubmed \| J Cardiovasc Med (Hagerstown))	Phase 3	Chronic heart failure	467	Canrenone	ixyozqgbsj(fhfreihslq) = fcqudnijyh dvabxzlwpf (iivgtbctkr ) View more	-	01 Sep 2007
				Placebo	ixyozqgbsj(fhfreihslq) = typangigny dvabxzlwpf (iivgtbctkr ) View more