| Title |
Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis
|
|---|---|
| Published in |
Clinical Pharmacokinetics, August 2016
|
| DOI | 10.1007/s40262-016-0433-0 |
| Pubmed ID | |
| Authors |
Raju Subramanian, Xiaochun Zhu, M. Benjamin Hock, Bethlyn J. Sloey, Benjamin Wu, Sarah F. Wilson, Ogo Egbuna, J. Greg Slatter, Jim Xiao, Gary L. Skiles |
| Abstract |
Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [(14)C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting. Blood, dialysate, urine, and feces were collected to characterize the pharmacokinetics, biotransformation product profiles, mass balance, and formation of anti-etelcalcetide antibodies. Accelerator mass spectrometry was necessary to measure the microtracer quantities of C-14 excreted in the large volumes of dialysate and other biomatrices. An estimated 67 % of the [(14)C]etelcalcetide dose was recovered in dialysate, urine, and feces 176 days after dose administration. Etelcalcetide was primarily cleared by hemodialysis, with approximately 60 % of the administered dose eliminated in dialysate. Minor excretion was observed in urine and feces. Biotransformation resulted from disulfide exchange with endogenous thiols, and preserved the etelcalcetide D-amino acid backbone. Drug-related radioactivity circulated primarily as serum albumin peptide conjugate (SAPC). Following removal of plasma etelcalcetide by hemodialysis, re-equilibration occurred between SAPC and L-cysteine present in blood to partially restore the etelcalcetide plasma concentrations between dialysis sessions. No unanticipated safety signals or anti-etelcalcetide or anti-SAPC antibodies were detected. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 20% |
| Student > Ph. D. Student | 5 | 13% |
| Student > Bachelor | 4 | 10% |
| Student > Postgraduate | 4 | 10% |
| Student > Doctoral Student | 3 | 8% |
| Other | 3 | 8% |
| Unknown | 13 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 14 | 35% |
| Agricultural and Biological Sciences | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
| Nursing and Health Professions | 2 | 5% |
| Biochemistry, Genetics and Molecular Biology | 1 | 3% |
| Other | 4 | 10% |
| Unknown | 13 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 January 2023.
All research outputs
#3,069,650
of 23,565,002 outputs
Outputs from Clinical Pharmacokinetics
#136
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Outputs of similar age
#56,198
of 358,305 outputs
Outputs of similar age from Clinical Pharmacokinetics
#3
of 22 outputs
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So far Altmetric has tracked 1,519 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one has done well, scoring higher than 89% of its peers.
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