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Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification

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dc.contributor.authorFerrer, Miguel D
dc.contributor.authorKetteler, Markus
dc.contributor.authorTur, Fernando
dc.contributor.authorTur, Eva
dc.contributor.authorIsern, Bernet
dc.contributor.authorSalcedo, Carolina
dc.contributor.authorJoubert, Pieter H
dc.contributor.authorBehets, Geert J
dc.contributor.authorNeven, Ellen
dc.contributor.authorD'Haese, Patrick C
dc.contributor.authorPerello, Joan
dc.date.accessioned2024-09-06T09:56:04Z
dc.date.available2024-09-06T09:56:04Z
dc.date.issued2018-05-09
dc.description.abstractEnd-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. SNF472 was studied in three rat models: (1) prevention of vitamin D-3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D-3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. Uremic rats presented lower plasma levels of SNF472 than control animals after i.v. infusion. CVC in non-uremic rats was inhibited by 60-70% after treatment with SNF472 and progression of cardiac calcification completely blocked. Development of CVC in uremic rats was inhibited by up to 80% following i.v. infusion of SNF472. SNF472 inhibits the development and progression of CVC in uremic and non-uremic rats in the same range of SNF472 plasma levels but using in each case the required dose to obtain those levels. These results collectively support the development of SNF472 as a novel therapeutic option for treatment of CVC in humans.en
dc.description.sponsorshipThis study was supported by a grant from Fundacion Genoma Espana/Centro para el Desarrollo Tecnologico Industrial (CDTI) through the INNOCASH program (IC10- 129) and from private funds of Laboratoris Sanifit. MF (PTQ-11-04860), ET (PTQ-09-01-00301) and CS (PTQ-11-04872) were co-funded by the INNCORPORA-Torres Quevedo subprogram of the Ministerio de Economia y Competitividad, Government of Spain. The funders (Fundacion Genoma Espana/CDTI, Ministerio de Economia y Competitividad, the investors of Laboratoris Sanifit) provided support in the form of salaries for authors [MF, FT, ET, BI, CS, PJ, JP], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.es_ES
dc.format.number5es_ES
dc.format.page197061es_ES
dc.format.volume13es_ES
dc.identifier.citationFerrer MD, Ketteler M, Tur F, Tur E, Isern B, Salcedo C, et al. Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification. PLoS One. 2018 May 09;13(5):197061.en
dc.identifier.doi10.1371/journal.pone.0197061
dc.identifier.issn1932-6203
dc.identifier.journalPloS Onees_ES
dc.identifier.otherhttp://hdl.handle.net/20.500.13003/9301
dc.identifier.pubmedID29742152es_ES
dc.identifier.puiL622059465
dc.identifier.scopus2-s2.0-85046770456
dc.identifier.urihttps://hdl.handle.net/20.500.12105/22602
dc.identifier.wos431757400059
dc.language.isoengen
dc.publisherPublic Library of Science (PLOS)
dc.relation.publisherversionhttps://dx.doi.org/10.1371/journal.pone.0197061en
dc.rights.accessRightsopen accessen
dc.rights.licenseAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.decsAnimales*
dc.subject.decsCalcinosis*
dc.subject.decsRatas*
dc.subject.decsColecalciferol*
dc.subject.decsHumanos*
dc.subject.decsFallo Renal Crónico*
dc.subject.decsUremia*
dc.subject.decsProgresión de la Enfermedad*
dc.subject.decsInsuficiencia Renal Crónica*
dc.subject.decsEnfermedades Cardiovasculares*
dc.subject.decsInositol*
dc.subject.decsModelos Animales de Enfermedad*
dc.subject.meshCardiovascular Diseases*
dc.subject.meshDisease Models, Animal*
dc.subject.meshDisease Progression*
dc.subject.meshInositol*
dc.subject.meshRats*
dc.subject.meshAnimals*
dc.subject.meshCholecalciferol*
dc.subject.meshHumans*
dc.subject.meshCalcinosis*
dc.subject.meshKidney Failure, Chronic*
dc.subject.meshRenal Insufficiency, Chronic*
dc.subject.meshUremia*
dc.titleCharacterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcificationen
dc.typeresearch articleen
dspace.entity.typePublication
relation.isPublisherOfPublicationa2759e3d-0d58-4e8a-9fcd-c6130ee333d1
relation.isPublisherOfPublication.latestForDiscoverya2759e3d-0d58-4e8a-9fcd-c6130ee333d1

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