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In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins

Immunoglobulin replacement therapy is a life-saving treatment in patients with immunodeficiency and effective in the management of autoimmune disorders. Immunoglobulins are administered intravenously or subcutaneously, with the latter route reducing systemic reactions and providing an option for sel...

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Autores principales: Leidenmühler, Peter, Höfinghoff, Joris, Haider, Norbert, Brachtl, Gerald, Weiller, Markus, Bilic, Ivan, Gangadharan, Bagirath
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382333/
https://www.ncbi.nlm.nih.gov/pubmed/36920736
http://dx.doi.org/10.1007/s13346-023-01321-y
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author Leidenmühler, Peter
Höfinghoff, Joris
Haider, Norbert
Brachtl, Gerald
Weiller, Markus
Bilic, Ivan
Gangadharan, Bagirath
author_facet Leidenmühler, Peter
Höfinghoff, Joris
Haider, Norbert
Brachtl, Gerald
Weiller, Markus
Bilic, Ivan
Gangadharan, Bagirath
author_sort Leidenmühler, Peter
collection PubMed
description Immunoglobulin replacement therapy is a life-saving treatment in patients with immunodeficiency and effective in the management of autoimmune disorders. Immunoglobulins are administered intravenously or subcutaneously, with the latter route reducing systemic reactions and providing an option for self-infusion, increasing patient convenience, while decreasing patient burden, healthcare utilization, and costs. A major limitation with subcutaneous administrations is the frequency of infusion due to limited volumes administrable into subcutaneous space, necessitating increased drug concentration, absorption, and dispersion. Increasing the concentration of immunoglobulins from 10 to 20% halves the required volume, but leads to higher dynamic viscosity, limiting infusion rate. Recombinant human hyaluronidase increases dispersion and absorption of immunoglobulins allowing administration of ≤ 600 mL per site, but does not change viscosity. Since the viscosity of fluids depends on temperature, we tested the feasibility of in-line warming of immunoglobulin formulations to physiological temperatures. In vitro analysis showed no negative impact of in-line warming to 38 °C on product quality. Subcutaneous infusion studies in pigs confirmed the feasibility of infusion rates of up to 7.5 mL/min with in-line warmed TAK-881, an immunoglobulin 20% facilitated with recombinant human hyaluronidase. In-line pressures were reduced compared with conventional immunoglobulin 20%, and local tolerance was not altered. Reduction of in-line pressures was more pronounced with thinner needle sets, indicating a potential benefit for patients. In summary, an in in-line warming device can circumvent the limitation of high viscosity, while product quality and local tolerance are maintained. The results of the presented studies warrant further testing in a phase 1 clinical study. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-023-01321-y.
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spelling pubmed-103823332023-07-30 In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins Leidenmühler, Peter Höfinghoff, Joris Haider, Norbert Brachtl, Gerald Weiller, Markus Bilic, Ivan Gangadharan, Bagirath Drug Deliv Transl Res Original Article Immunoglobulin replacement therapy is a life-saving treatment in patients with immunodeficiency and effective in the management of autoimmune disorders. Immunoglobulins are administered intravenously or subcutaneously, with the latter route reducing systemic reactions and providing an option for self-infusion, increasing patient convenience, while decreasing patient burden, healthcare utilization, and costs. A major limitation with subcutaneous administrations is the frequency of infusion due to limited volumes administrable into subcutaneous space, necessitating increased drug concentration, absorption, and dispersion. Increasing the concentration of immunoglobulins from 10 to 20% halves the required volume, but leads to higher dynamic viscosity, limiting infusion rate. Recombinant human hyaluronidase increases dispersion and absorption of immunoglobulins allowing administration of ≤ 600 mL per site, but does not change viscosity. Since the viscosity of fluids depends on temperature, we tested the feasibility of in-line warming of immunoglobulin formulations to physiological temperatures. In vitro analysis showed no negative impact of in-line warming to 38 °C on product quality. Subcutaneous infusion studies in pigs confirmed the feasibility of infusion rates of up to 7.5 mL/min with in-line warmed TAK-881, an immunoglobulin 20% facilitated with recombinant human hyaluronidase. In-line pressures were reduced compared with conventional immunoglobulin 20%, and local tolerance was not altered. Reduction of in-line pressures was more pronounced with thinner needle sets, indicating a potential benefit for patients. In summary, an in in-line warming device can circumvent the limitation of high viscosity, while product quality and local tolerance are maintained. The results of the presented studies warrant further testing in a phase 1 clinical study. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-023-01321-y. Springer US 2023-03-15 2023 /pmc/articles/PMC10382333/ /pubmed/36920736 http://dx.doi.org/10.1007/s13346-023-01321-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Leidenmühler, Peter
Höfinghoff, Joris
Haider, Norbert
Brachtl, Gerald
Weiller, Markus
Bilic, Ivan
Gangadharan, Bagirath
In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
title In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
title_full In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
title_fullStr In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
title_full_unstemmed In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
title_short In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
title_sort in-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382333/
https://www.ncbi.nlm.nih.gov/pubmed/36920736
http://dx.doi.org/10.1007/s13346-023-01321-y
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