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A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody
PURPOSE: To review pharmacokinetic and pharmacodynamic characteristics of antibodies that bind to soluble ligands within the framework of calcitonin gene-related peptide antibodies. OVERVIEW: Calcitonin gene-related peptide has been implicated in the pathophysiology of migraine. Galcanezumab is an a...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710614/ https://www.ncbi.nlm.nih.gov/pubmed/30917684 http://dx.doi.org/10.1177/0333102419840780 |
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author | Kielbasa, William Helton, Danielle L |
author_facet | Kielbasa, William Helton, Danielle L |
author_sort | Kielbasa, William |
collection | PubMed |
description | PURPOSE: To review pharmacokinetic and pharmacodynamic characteristics of antibodies that bind to soluble ligands within the framework of calcitonin gene-related peptide antibodies. OVERVIEW: Calcitonin gene-related peptide has been implicated in the pathophysiology of migraine. Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide. Other antibodies that target calcitonin gene-related peptide include eptinezumab and fremanezumab. To understand how antibodies can affect the extent and duration of free ligand concentrations, it is important to consider the dose and pharmacokinetics of an antibody, and the kinetics of the ligand and antibody–ligand complex. Insights regarding the pharmacokinetic/pharmacodynamic properties of galcanezumab as a probe antibody drug and calcitonin gene-related peptide as its binding ligand regarding its clinical outcomes are provided. DISCUSSION: Antibodies are administered parenterally because oral absorption is limited by gastrointestinal degradation and inefficient diffusion through the epithelium. The systemic absorption of antibodies following intramuscular or subcutaneous administration most likely occurs via convective transport through lymphatic vessels into blood. The majority of antibody elimination occurs via intracellular catabolism into peptides and amino acids following endocytosis. Binding of ligand to an antibody reduces the free ligand that is available to interact with the receptor and efficacy is driven by the magnitude and duration of the reduction in free ligand concentration. A galcanezumab pharmacokinetic/pharmacodynamic model shows that galcanezumab decreases free calcitonin gene-related peptide concentrations in a dose- and time-dependent manner and continues to suppress free calcitonin gene-related peptide with repeated dosing. The model provides evidence for a mechanistic linkage to galcanezumab therapeutic effects for the preventive treatment of migraine. |
format | Online Article Text |
id | pubmed-6710614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-67106142019-09-17 A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody Kielbasa, William Helton, Danielle L Cephalalgia Review PURPOSE: To review pharmacokinetic and pharmacodynamic characteristics of antibodies that bind to soluble ligands within the framework of calcitonin gene-related peptide antibodies. OVERVIEW: Calcitonin gene-related peptide has been implicated in the pathophysiology of migraine. Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide. Other antibodies that target calcitonin gene-related peptide include eptinezumab and fremanezumab. To understand how antibodies can affect the extent and duration of free ligand concentrations, it is important to consider the dose and pharmacokinetics of an antibody, and the kinetics of the ligand and antibody–ligand complex. Insights regarding the pharmacokinetic/pharmacodynamic properties of galcanezumab as a probe antibody drug and calcitonin gene-related peptide as its binding ligand regarding its clinical outcomes are provided. DISCUSSION: Antibodies are administered parenterally because oral absorption is limited by gastrointestinal degradation and inefficient diffusion through the epithelium. The systemic absorption of antibodies following intramuscular or subcutaneous administration most likely occurs via convective transport through lymphatic vessels into blood. The majority of antibody elimination occurs via intracellular catabolism into peptides and amino acids following endocytosis. Binding of ligand to an antibody reduces the free ligand that is available to interact with the receptor and efficacy is driven by the magnitude and duration of the reduction in free ligand concentration. A galcanezumab pharmacokinetic/pharmacodynamic model shows that galcanezumab decreases free calcitonin gene-related peptide concentrations in a dose- and time-dependent manner and continues to suppress free calcitonin gene-related peptide with repeated dosing. The model provides evidence for a mechanistic linkage to galcanezumab therapeutic effects for the preventive treatment of migraine. SAGE Publications 2019-03-27 2019-09 /pmc/articles/PMC6710614/ /pubmed/30917684 http://dx.doi.org/10.1177/0333102419840780 Text en © International Headache Society 2019 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Review Kielbasa, William Helton, Danielle L A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody |
title | A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody |
title_full | A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody |
title_fullStr | A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody |
title_full_unstemmed | A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody |
title_short | A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody |
title_sort | new era for migraine: pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-cgrp antibody |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710614/ https://www.ncbi.nlm.nih.gov/pubmed/30917684 http://dx.doi.org/10.1177/0333102419840780 |
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