2026-04-29T02:37:44Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/226022024-11-29T00:46:09Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Ferrer, Miguel D author Ketteler, Markus author Tur, Fernando author Tur, Eva author Isern, Bernet author Salcedo, Carolina author Joubert, Pieter H author Behets, Geert J author Neven, Ellen author D'Haese, Patrick C author Perello, Joan author 2018-05-09 End-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. Ferrer 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. 1932-6203 http://hdl.handle.net/20.500.13003/9301 https://hdl.handle.net/20.500.12105/22602 29742152 10.1371/journal.pone.0197061 PloS One 2-s2.0-85046770456 431757400059 L622059465 Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification