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10.1124/jpet.113.204834

http://scihub22266oqcxt.onion/10.1124/jpet.113.204834
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suck abstract from ncbi

pmid23674604
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  • Pharmacology of AMG 416 (Velcalcetide), a novel peptide agonist of the calcium-sensing receptor, for the treatment of secondary hyperparathyroidism in hemodialysis patients #MMPMID23674604
  • Walter S; Baruch A; Dong J; Tomlinson JE; Alexander ST; Janes J; Hunter T; Yin Q; Maclean D; Bell G; Mendel DB; Johnson RM; Karim F
  • J Pharmacol Exp Ther 2013[Aug]; 346 (2): 229-40 PMID23674604show ga
  • A novel peptide, AMG 416 (formerly KAI-4169, and with a United States Adopted Name: velcalcetide), has been identified that acts as an agonist of the calcium-sensing receptor (CaSR). This article summarizes the in vitro and in vivo characterization of AMG 416 activity and the potential clinical utility of this novel compound. AMG 416 activates the human CaSR in vitro, acting by a mechanism distinct from that of cinacalcet, the only approved calcimimetic, since it can activate the CaSR both in the presence or the absence of physiologic levels of extracellular calcium. Administration of AMG 416 in vivo into either normal or renally compromised rats results in dose-dependent reductions in parathyroid hormone (PTH) levels and corresponding decreases in serum calcium, regardless of the baseline level of PTH. Treatment of 5/6 nephrectomized rats with AMG 416 resulted in dramatic improvements in their metabolic profile, including lower PTH and serum creatinine levels, reduced amounts of vascular calcification, attenuated parathyroid hyperplasia, and greater expression of the parathyroid gland regulators CaSR, vitamin D receptor, and FGF23 receptor compared with vehicle-treated animals. No drug accumulation was observed under this dosing regimen, and the terminal half-life of AMG 416 was estimated to be 2-4.5 hours. As a long-acting CaSR agonist, AMG 416 is an innovative new therapy for the treatment of hemodialysis patients with secondary hyperparathyroidism.
  • |Animals[MESH]
  • |Female[MESH]
  • |Fibroblast Growth Factor-23[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Hyperparathyroidism, Secondary/*drug therapy/etiology/metabolism[MESH]
  • |Kidney/physiopathology[MESH]
  • |Male[MESH]
  • |Nephrectomy[MESH]
  • |Parathyroid Glands/drug effects/metabolism[MESH]
  • |Parathyroid Hormone/blood[MESH]
  • |Peptides/pharmacokinetics/pharmacology/*therapeutic use[MESH]
  • |Rats[MESH]
  • |Rats, Sprague-Dawley[MESH]
  • |Receptors, Calcium-Sensing/*agonists[MESH]
  • |Renal Dialysis/adverse effects[MESH]
  • |Tissue Distribution[MESH]
  • |Uremia/drug therapy/etiology[MESH]


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  • suck abstract from ncbi

    229 2.346 2013