Direct Drug Delivery of Low-Permeable Compounds to the Central Nervous System Via Intranasal Administration in Rats and Monkeys.
Pharm Res
; 36(5): 76, 2019 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-30937626
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Preparações Farmacêuticas
/
Barreira Hematoencefálica
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Sistemas de Liberação de Medicamentos
Limite:
Animals
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão