Clinical Pharmacokinetics and Pharmacodynamics of Etelcalcetide, a Novel Calcimimetic for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis.

Autor: Wu B; Amgen Inc., Thousand Oaks, CA, USA., Melhem M; Amgen Inc., Thousand Oaks, CA, USA., Subramanian R; Amgen Inc., Thousand Oaks, CA, USA., Chen P; Amgen Inc., Thousand Oaks, CA, USA., Jaramilla Sloey B; Amgen Inc., Thousand Oaks, CA, USA., Fouqueray B; Amgen Inc., Thousand Oaks, CA, USA., Hock MB; Amgen Inc., Thousand Oaks, CA, USA., Skiles GL; Amgen Inc., Thousand Oaks, CA, USA., Chow AT; Amgen Inc., Thousand Oaks, CA, USA., Lee E; Amgen Inc., Thousand Oaks, CA, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2018 Jun; Vol. 58 (6), pp. 717-726. Date of Electronic Publication: 2018 Mar 13.
DOI: 10.1002/jcph.1090
Abstrakt: Etelcalcetide, a d-amino acid peptide, is an intravenous calcimimetic approved for the treatment of secondary hyperparathyroidism. Etelcalcetide binds the calcium-sensing receptor and increases its sensitivity to extracellular calcium, thereby decreasing secretion of parathyroid hormone (PTH) by chief cells. Etelcalcetide and its low-molecular-weight transformation products are rapidly cleared by renal excretion in healthy subjects, but clearance is substantially reduced and dependent on hemodialysis in end-stage renal disease. The effective half-life is 3-5 days in patients undergoing hemodialysis 3 times a week. A clinical study using a single microtracer intravenous dose of [ 14 C]etelcalcetide indicated that 60% of the administered dose was eliminated in dialysate. Etelcalcetide undergoes reversible disulfide exchange with serum albumin to form a serum albumin peptide conjugate that is too large (67 kDa) to be dialyzed, until a subsequent exchange forms etelcalcetide or a low-molecular-weight transformation product. This exchange from albumin is apparent after hemodialysis, when it partially restores etelcalcetide concentrations in plasma. Etelcalcetide has no known risks for drug-drug interactions. In phase 3 studies, 74%-75% of hemodialysis patients with secondary hyperparathyroidism who received etelcalcetide achieved a >30% PTH reduction from baseline versus 8%-10% of patients who received placebo. The pharmacokinetics and pharmacodynamics of etelcalcetide in hemodialysis patients supports a 5-mg starting dose administered after hemodialysis and uptitration in 2.5- or 5-mg increments every 4 weeks to a maximum dose of 15 mg 3 times a week.
(© 2018, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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