title: Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting.
abstract: The currently available antiepileptic drugs are typically administered via oral or intravenous (IV) routes which commonly exhibit high systemic distribution into non-targeted tissues, leading to peripheral adverse effects and limited brain uptake. In order to improve the efficacy and tolerability of the antiepileptic drug therapy, alternative administration strategies have been investigated. The purpose of the present study was to assess the pharmacokinetics of carbamazepine administered via intranasal (IN) and IV routes to mice, and to investigate whether a direct transport of the drug from nose to brain could be involved. The similar pharmacokinetic profiles obtained in all matrices following both administration routes indicate that, after IN delivery, carbamazepine reaches quickly and extensively the bloodstream, achieving the brain predominantly via systemic circulation. However, the uneven biodistribution of carbamazepine through the brain regions with higher concentrations in the olfactory bulb and frontal cortex following IN instillation, in comparison with the homogenous brain distribution pattern after IV injection, strongly suggests the involvement of a direct transport of carbamazepine from nose to brain. Therefore, it seems that IN delivery represents a suitable and promising alternative route to administer carbamazepine not only for the chronically use of the drug but also in emergency conditions.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Serralheiro
authors.affiliation: CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal. Electronic address: gilberto@fcsaude.ubi.pt.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Alves
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuna
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Centre for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
mesh_terms: D000281:Administration, Intranasal; D061605:Administration, Intravenous; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D002220:Carbamazepine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine
keywords: Brain distribution; Carbamazepine; Intranasal administration; Mice; Nose-to-brain drug delivery; Pharmacokinetics