Hydroxocobalamin Uptake into the Cerebrospinal Fluid after Nasal and Intravenous Delivery in Rats and Humans |
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| Authors: | Mascha P. Van den berg Paul Merkus Stefan G. Romeijn J. Coos Verhoef Frans W.H.M. Merkus |
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| Affiliation: | 1. Division of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlandsf.merkus@lacdr.leidenuniv.nl;3. Department of Oto-Rhino-Laryngology, Vrije Universiteit Medical Centre, Head and Neck surgery, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands;4. Division of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands |
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| Abstract: | The possibility of direct transport of hydroxocobalamin from the nasal cavity into the cerebrospinal fluid (CSF) after nasal administration in rats was investigated and the results were compared with a human study.Hydroxocobalamin was given to rats (n=8) both intranasally (214 μg/rat) and intravenously (49.5 μg/rat) into the jugular vein using a Vascular Access Port (VAP). Prior to and after drug administration, blood and CSF samples were taken and analysed by radioimmunoassay.The AUCCSF/AUCplasma ratio after nasal delivery does not differ from the ratio after intravenous infusion, indicating that hydroxocobalamin enters the CSF via the blood circulation across the blood–brain barrier (BBB). This same transport route is confirmed by the cumulative AUC-time profiles in CSF and plasma, demonstrating a 30 min delay between plasma absorption and CSF uptake of hydroxocobalamin in rats and in a comparative human study.The present results in rats show that there is no additional uptake of hydroxocobalamin in the CSF after nasal delivery compared to intravenous administration, which is in accordance with the results found in humans. This indicates a predictive value of the used rat model for the human situation when studying the nose to CSF transport of drugs. |
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| Keywords: | Hydroxocobalamin Intranasal delivery Intravenous infusion Cerebrospinal fluid Rat Human |
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