Direct Drug Delivery of Low-Permeable Compounds to the Central Nervous System Via Intranasal Administration in Rats and Monkeys View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-05

AUTHORS

Shinji Iwasaki, Syunsuke Yamamoto, Noriyasu Sano, Kimio Tohyama, Yohei Kosugi, Atsutoshi Furuta, Teruki Hamada, Tomoko Igari, Yasushi Fujioka, Hideki Hirabayashi, Nobuyuki Amano

ABSTRACT

PURPOSE: Intranasal administration enhances drug delivery to the brain by allowing targeted-drug delivery. Here, we investigated the properties that render a compound suitable for intranasal administration, and the differences between rodents and non-human primates in delivery to the brain. METHODS: The delivery of 10 low-permeable compounds to the brain, including substrates of efflux drug transporters expressed in the blood-brain barrier (didanosine, metformin, zolmitriptan, cimetidine, methotrexate, talinolol, ranitidine, atenolol, furosemide, and sulpiride) and two high-permeable compounds (ropinirole and midazolam) was evaluated following intranasal and intravenous administration in rats. Six of the 12 compounds (metformin, cimetidine, methotrexate, talinolol, sulpiride, and ropinirole) were also evaluated in monkeys, which have a similar nasal cavity anatomical structure to humans. RESULTS: In rats, most of the low-permeable compounds displayed an obvious increase in the brain/plasma concentration ratio (Kp) by intranasal administration (despite their substrate liability for efflux drug transporters); this was not observed with the high-permeable compounds. Similarly, intranasal administration increased Kp for all low-permeable compounds in monkeys. CONCLUSIONS: Compound permeability is a key determinant of Kp increase by intranasal administration. This route of administration is more beneficial for low-permeable compounds and enhances their delivery to the brain in rodents and non-human primates. More... »

PAGES

76

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11095-019-2613-8

DOI

http://dx.doi.org/10.1007/s11095-019-2613-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113173562

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30937626


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s11095-019-2613-8'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s11095-019-2613-8'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s11095-019-2613-8'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s11095-019-2613-8'


 

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