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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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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. |
format | Online Article Text |
id | pubmed-4303928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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