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

Molecular FormulaC22H28O3

InChIKeyUJVLDDZCTMKXJK-WNHSNXHDSA-N

CAS Registry976-71-6

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.

01 Mar 2024·Archives of Toxicology

Probing the hair detectability of prohibited substances in sports: an in vivo-in silico-clinical approach and analytical implications compared with plasma, urine, and faeces

Article

Author: Lin, Yi-Ching ; Hung, Shao-Hsin ; Chang, William Chih-Wei ; Tian, Ciao ; Tung, Chun-Wei ; Kan, Hung-Lin ; Chen, Ting-Ting

AbstractHair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency’s List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography–tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.

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


NCT02687178 (ESCAPE-IT, Pubmed \| Cardiovasc Ther)	Phase 4	Hypertension Add-on	175	Canrenone 50 mg	iifcoveijw(cfadcfzofx) = puagraccon omjcyytrca (fjadaofhzq ) View more	-	01 Feb 2017
				Canrenone 100 mg	iifcoveijw(cfadcfzofx) = wmaqpkdmpu omjcyytrca (fjadaofhzq ) View more
NCT00403910 (AREA IN-CHF, Pubmed \| Eur J Heart Fail)	Phase 3	Chronic heart failure	-	Canrenone	(qjrvvdmwqq) = ocrpiaygdf vsvzrufvvz (qwhlvrednf ) View more	-	01 Jan 2009
				Placebo	(qjrvvdmwqq) = adijkholmj vsvzrufvvz (qwhlvrednf ) View more
NCT00403910 (AREA IN-CHF, Pubmed \| J Cardiovasc Med (Hagerstown))	Phase 3	Chronic heart failure	467	Canrenone	(zuiwbwqqko) = rrvzqkpbcx gphtukwnor (mjuekzowdc ) View more	-	01 Sep 2007
				Placebo	(zuiwbwqqko) = dgmnwqefqm gphtukwnor (mjuekzowdc ) View more