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Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function

Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacologi...

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Autores principales: Hu, Xiao, Seddighzadeh, Ali, Stecher, Scott, Zhu, Ying, Goyal, Jaya, Matson, Mark, Marbury, Thomas, Smith, William, Nestorov, Ivan, Hung, Serena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303928/
https://www.ncbi.nlm.nih.gov/pubmed/25187030
http://dx.doi.org/10.1002/jcph.390
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author Hu, Xiao
Seddighzadeh, Ali
Stecher, Scott
Zhu, Ying
Goyal, Jaya
Matson, Mark
Marbury, Thomas
Smith, William
Nestorov, Ivan
Hung, Serena
author_facet Hu, Xiao
Seddighzadeh, Ali
Stecher, Scott
Zhu, Ying
Goyal, Jaya
Matson, Mark
Marbury, Thomas
Smith, William
Nestorov, Ivan
Hung, Serena
author_sort Hu, Xiao
collection PubMed
description Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) of peginterferon beta-1a following a single subcutaneous dose at 63 μg (n = 5) or 125 μg (n = 30). The results showed a fractional increase in area-under-the-concentration-time curve (AUC [30–53%]) and peak serum concentration (C(max) [26–42%]) in subjects with mild, moderate, and severe renal impairment, versus healthy subjects; AUC and C(max) were similar for healthy subjects and end-stage-renal-disease patients receiving hemodialysis. Pharmacokinetic simulation showed that the steady state concentration overlapped in the majority of healthy subjects and subjects with severe renal impairment. Neopterin baseline, peak concentration, and AUC increased as renal function decreased. Peginterferon beta-1a was well tolerated in all groups. These results do not warrant peginterferon beta-1a dose adjustment in subjects with renal impairment.
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spelling pubmed-43039282015-02-02 Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function Hu, Xiao Seddighzadeh, Ali Stecher, Scott Zhu, Ying Goyal, Jaya Matson, Mark Marbury, Thomas Smith, William Nestorov, Ivan Hung, Serena J Clin Pharmacol Special Populations Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) of peginterferon beta-1a following a single subcutaneous dose at 63 μg (n = 5) or 125 μg (n = 30). The results showed a fractional increase in area-under-the-concentration-time curve (AUC [30–53%]) and peak serum concentration (C(max) [26–42%]) in subjects with mild, moderate, and severe renal impairment, versus healthy subjects; AUC and C(max) were similar for healthy subjects and end-stage-renal-disease patients receiving hemodialysis. Pharmacokinetic simulation showed that the steady state concentration overlapped in the majority of healthy subjects and subjects with severe renal impairment. Neopterin baseline, peak concentration, and AUC increased as renal function decreased. Peginterferon beta-1a was well tolerated in all groups. These results do not warrant peginterferon beta-1a dose adjustment in subjects with renal impairment. BlackWell Publishing Ltd 2015-02 2014-09-23 /pmc/articles/PMC4303928/ /pubmed/25187030 http://dx.doi.org/10.1002/jcph.390 Text en © 2014, The American College of Clinical Pharmacology
spellingShingle Special Populations
Hu, Xiao
Seddighzadeh, Ali
Stecher, Scott
Zhu, Ying
Goyal, Jaya
Matson, Mark
Marbury, Thomas
Smith, William
Nestorov, Ivan
Hung, Serena
Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function
title Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function
title_full Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function
title_fullStr Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function
title_full_unstemmed Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function
title_short Pharmacokinetics, Pharmacodynamics, and Safety of Peginterferon Beta-Ia in Subjects with Normal or Impaired Renal Function
title_sort pharmacokinetics, pharmacodynamics, and safety of peginterferon beta-ia in subjects with normal or impaired renal function
topic Special Populations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303928/
https://www.ncbi.nlm.nih.gov/pubmed/25187030
http://dx.doi.org/10.1002/jcph.390
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