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 (2019). A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs. Journal of biological methods, 6(1), e107. POL Scientific, LLC 10.14440/jbm.2019.265

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Central Animal Facility
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Bergadano, Alessandra

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2326-9901

Publisher:

POL Scientific, LLC

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

17 Dec 2019 13:45

Last Modified:

17 Dec 2019 13:45

Publisher DOI:

10.14440/jbm.2019.265

PubMed ID:

31453257

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.136196

URI:

https://boris.unibe.ch/id/eprint/136196

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