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A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs
Drug concentrations in cerebrospinal fluid (CSF) are typically used as a as a surrogate measure of their availability in the CNS, and CSF penetration in animal studies are used for assessment of CNS drug delivery in early preclinical drug development. The minipig is a valid alternative to dogs and n...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Journal of Biological Methods
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706129/ https://www.ncbi.nlm.nih.gov/pubmed/31453257 http://dx.doi.org/10.14440/jbm.2019.265 |
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author | Bergadano, Alessandra Amen, Eva Maria Jacobsen, Björn Belli, Sara Vandjour, Anthony Rapp, Christelle Senn, Claudia |
author_facet | Bergadano, Alessandra Amen, Eva Maria Jacobsen, Björn Belli, Sara Vandjour, Anthony Rapp, Christelle Senn, Claudia |
author_sort | Bergadano, Alessandra |
collection | PubMed |
description | Drug concentrations in cerebrospinal fluid (CSF) are typically used as a as a surrogate measure of their availability in the CNS, and CSF penetration in animal studies are used for assessment of CNS drug delivery in early preclinical drug development. The minipig is a valid alternative to dogs and non-human primates as non-rodent species in preclinical research, but this species presents anatomical peculiarities that make the serial collection of CSF technically challenging. A minimally-invasive serial cerebrospinal fluid collection model via catheterization of the subarachnoid space in conscious minipigs was developed allowing assessment of longitudinal drug pharmacokinetics in the central nervous system in preclinical research. Shortly, the subarachnoid space was accessed in the anesthetized minipig by puncture with a Tuohy needle; when CSF was flowing through the needle a catheter was advanced and thereafter tunneled and fixed on the back. The PK of peptide A administered subcutaneously was performed and CSF could be sampled in the conscious animals for up to 48 h. When compared to the plasma kinetic data, there was a clear difference in the elimination phase of Pept. A from CSF, with an apparent longer average terminal half-life in CSF. The 3Rs are addressed by reducing the number of animals needed for a pharmacokinetic profile in central nervous system and by improving the validity of the model avoiding biases due to anesthesia, blood contamination, and inter-individual variability. |
format | Online Article Text |
id | pubmed-6706129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Journal of Biological Methods |
record_format | MEDLINE/PubMed |
spelling | pubmed-67061292019-08-26 A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs Bergadano, Alessandra Amen, Eva Maria Jacobsen, Björn Belli, Sara Vandjour, Anthony Rapp, Christelle Senn, Claudia J Biol Methods Article Drug concentrations in cerebrospinal fluid (CSF) are typically used as a as a surrogate measure of their availability in the CNS, and CSF penetration in animal studies are used for assessment of CNS drug delivery in early preclinical drug development. The minipig is a valid alternative to dogs and non-human primates as non-rodent species in preclinical research, but this species presents anatomical peculiarities that make the serial collection of CSF technically challenging. A minimally-invasive serial cerebrospinal fluid collection model via catheterization of the subarachnoid space in conscious minipigs was developed allowing assessment of longitudinal drug pharmacokinetics in the central nervous system in preclinical research. Shortly, the subarachnoid space was accessed in the anesthetized minipig by puncture with a Tuohy needle; when CSF was flowing through the needle a catheter was advanced and thereafter tunneled and fixed on the back. The PK of peptide A administered subcutaneously was performed and CSF could be sampled in the conscious animals for up to 48 h. When compared to the plasma kinetic data, there was a clear difference in the elimination phase of Pept. A from CSF, with an apparent longer average terminal half-life in CSF. The 3Rs are addressed by reducing the number of animals needed for a pharmacokinetic profile in central nervous system and by improving the validity of the model avoiding biases due to anesthesia, blood contamination, and inter-individual variability. Journal of Biological Methods 2019-01-11 /pmc/articles/PMC6706129/ /pubmed/31453257 http://dx.doi.org/10.14440/jbm.2019.265 Text en © 2019 The Journal of Biological Methods, All rights reserved. https://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 License. |
spellingShingle | Article Bergadano, Alessandra Amen, Eva Maria Jacobsen, Björn Belli, Sara Vandjour, Anthony Rapp, Christelle Senn, Claudia A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs |
title | A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs |
title_full | A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs |
title_fullStr | A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs |
title_full_unstemmed | A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs |
title_short | A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs |
title_sort | minimally-invasive serial cerebrospinal fluid sampling model in conscious göttingen minipigs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706129/ https://www.ncbi.nlm.nih.gov/pubmed/31453257 http://dx.doi.org/10.14440/jbm.2019.265 |
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