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Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans
Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high‐affinity monoclonal antibody that neutralizes PA, is approved in t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668011/ https://www.ncbi.nlm.nih.gov/pubmed/29125719 http://dx.doi.org/10.1002/cpdd.410 |
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author | Nagy, Christa F. Leach, Timothy S. King, Alex Guttendorf, Robert |
author_facet | Nagy, Christa F. Leach, Timothy S. King, Alex Guttendorf, Robert |
author_sort | Nagy, Christa F. |
collection | PubMed |
description | Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high‐affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6–9 days, and terminal half‐life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection‐site abscesses or hypersensitivity reactions occurred; no subjects developed treatment‐emergent antitherapeutic antibodies over the study period of 71 days. |
format | Online Article Text |
id | pubmed-6668011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66680112019-08-06 Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans Nagy, Christa F. Leach, Timothy S. King, Alex Guttendorf, Robert Clin Pharmacol Drug Dev Articles Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high‐affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6–9 days, and terminal half‐life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection‐site abscesses or hypersensitivity reactions occurred; no subjects developed treatment‐emergent antitherapeutic antibodies over the study period of 71 days. John Wiley and Sons Inc. 2017-11-10 2018-08 /pmc/articles/PMC6668011/ /pubmed/29125719 http://dx.doi.org/10.1002/cpdd.410 Text en © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology This is an open access article under the terms of the 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 | Articles Nagy, Christa F. Leach, Timothy S. King, Alex Guttendorf, Robert Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans |
title | Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans |
title_full | Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans |
title_fullStr | Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans |
title_full_unstemmed | Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans |
title_short | Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans |
title_sort | safety, pharmacokinetics, and immunogenicity of obiltoxaximab after intramuscular administration to healthy humans |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668011/ https://www.ncbi.nlm.nih.gov/pubmed/29125719 http://dx.doi.org/10.1002/cpdd.410 |
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