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Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers
Ferric pyrophosphate citrate (Triferic) is a water‐soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double‐blind, randomized, placebo‐controlled, single‐, ascending‐dose study was conducted to evaluate the pharmacokinetics an...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324677/ https://www.ncbi.nlm.nih.gov/pubmed/27557937 http://dx.doi.org/10.1002/jcph.819 |
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author | Pratt, Raymond D. Swinkels, Dorine W. Ikizler, T. Alp Gupta, Ajay |
author_facet | Pratt, Raymond D. Swinkels, Dorine W. Ikizler, T. Alp Gupta, Ajay |
author_sort | Pratt, Raymond D. |
collection | PubMed |
description | Ferric pyrophosphate citrate (Triferic) is a water‐soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double‐blind, randomized, placebo‐controlled, single‐, ascending‐dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron‐replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFe(tot)), transferrin‐bound iron (TBI), hepcidin‐25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFe(tot) was observed in placebo‐treated subjects. Concentrations of sFe(tot) and TBI increased rapidly after drug administration, with maximum serum concentrations (C(max)) reached at the end of infusion. Increases in baseline‐corrected C(max) and area under the concentration‐time curve from 0 to the time of the last quantifiable concentration (AUC(0‐t)) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half‐life 1.2‐2 hours). No significant changes from baseline in serum hepcidin‐25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation. |
format | Online Article Text |
id | pubmed-5324677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53246772017-03-14 Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers Pratt, Raymond D. Swinkels, Dorine W. Ikizler, T. Alp Gupta, Ajay J Clin Pharmacol Pharmacokinetics Ferric pyrophosphate citrate (Triferic) is a water‐soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double‐blind, randomized, placebo‐controlled, single‐, ascending‐dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron‐replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFe(tot)), transferrin‐bound iron (TBI), hepcidin‐25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFe(tot) was observed in placebo‐treated subjects. Concentrations of sFe(tot) and TBI increased rapidly after drug administration, with maximum serum concentrations (C(max)) reached at the end of infusion. Increases in baseline‐corrected C(max) and area under the concentration‐time curve from 0 to the time of the last quantifiable concentration (AUC(0‐t)) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half‐life 1.2‐2 hours). No significant changes from baseline in serum hepcidin‐25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation. John Wiley and Sons Inc. 2016-10-03 2017-03 /pmc/articles/PMC5324677/ /pubmed/27557937 http://dx.doi.org/10.1002/jcph.819 Text en © 2016 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Pharmacokinetics Pratt, Raymond D. Swinkels, Dorine W. Ikizler, T. Alp Gupta, Ajay Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers |
title | Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers |
title_full | Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers |
title_fullStr | Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers |
title_full_unstemmed | Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers |
title_short | Pharmacokinetics of Ferric Pyrophosphate Citrate, a Novel Iron Salt, Administered Intravenously to Healthy Volunteers |
title_sort | pharmacokinetics of ferric pyrophosphate citrate, a novel iron salt, administered intravenously to healthy volunteers |
topic | Pharmacokinetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324677/ https://www.ncbi.nlm.nih.gov/pubmed/27557937 http://dx.doi.org/10.1002/jcph.819 |
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