Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity.

Autor: van den Berg MP; Department of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands., Romeijn SG, Verhoef JC, Merkus FW
Jazyk: angličtina
Zdroj: Journal of neuroscience methods [J Neurosci Methods] 2002 Apr 30; Vol. 116 (1), pp. 99-107.
DOI: 10.1016/s0165-0270(02)00033-x
Abstrakt: Drug transport from the nasal cavity to the brain has gained much interest in the last decade. In the present study, a model was developed to determine the uptake of drugs into the cerebrospinal fluid (CSF) after nasal delivery in rats. CSF samples were taken using a cisternal puncture method. In this method, a needle is advanced through the skin and muscles overlying the atlanto-occipital membrane into the cisterna magna, while the rat is fixed in a stereotaxic frame. This method appears to be superior over cannulation of the atlanto-occipital membrane for CSF sampling. The major advantages of the puncture method is the ability of serial and simultaneous CSF and blood sampling for over 2 h in the same rat. To obtain maximal drug absorption from the nasal cavity and uptake into CSF, different positions of the rat's head (upright-90 degrees, supine-90 degrees, supine-45 degrees and supine-70 degrees angles) were tested in nasal delivery studies using hydrocortisone (HC) as a model drug. Putting the rat in the supine-90 degrees angle position increased the absorption of HC into plasma and CSF 2-fold compared to the upright-90 degrees angle position. The supine-70 degrees angle position did not change the HC plasma and CSF levels compared to the supine-90 degrees angle position. However, the supine-70 degrees angle position showed the fastest CSF sampling rate, enabling more accurate CSF sampling and therefore preferred for further studies. In conclusion, the cisternal puncture method using the supine-70 degrees and 90 degrees angle position is a suitable method to study drug transport from the nasal cavity into the CSF, with the ability of multiple CSF sampling.
Databáze: MEDLINE
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