A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs

Authors

  • Alessandra Bergadano Department for BioMedical Research, University of Bern
  • Eva Maria Amen Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Björn Jacobsen Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Sara Belli Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Anthony Vandjour Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Christelle Rapp Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland
  • Claudia Senn Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland

DOI:

https://doi.org/10.14440/jbm.2019.265

Keywords:

CSF collection, Göttingen minipig, in vivo study, longitudinal CSF PK study, minimally-invasive model

Abstract

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.

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Published

2019-01-11

How to Cite

1.
Bergadano A, Amen EM, Jacobsen B, Belli S, Vandjour A, Rapp C, Senn C. A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs. J Biol Methods [Internet]. 2019Jan.11 [cited 2021Dec.3];6(1):e107. Available from: https://jbmethods.org/jbm/article/view/265

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