title: Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity.
abstract: 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.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors: Mascha P
authors: MP
authors: van den Berg
authors: Stefan G
authors: SG
authors: Romeijn
authors: J Coos
authors: JC
authors: Verhoef
authors: Frans W H M
authors: FW
authors: Merkus
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D002946:Cisterna Magna; D006854:Hydrocortisone / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D008297:Male; D009296:Nasal Cavity / Q000378:metabolism*; D011187:Posture; D051381:Rats; D017208:Rats, Wistar; D013129:Spinal Puncture / Q000379:methods*; D013238:Stereotaxic Techniques
chemical_list: D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone