Serralheiro Ana, Alves Gilberto, Fortuna Ana, Falcão Amílcar
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.
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.
Eur J Pharm Sci. 2014 Aug 18;60:32-9. doi: 10.1016/j.ejps.2014.04.019. Epub 2014 May 9.
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.
目前可用的抗癫痫药物通常通过口服或静脉注射途径给药，这些途径通常会在非靶向组织中表现出较高的全身分布，从而导致外周不良反应和有限的脑摄取。为了提高抗癫痫药物治疗的疗效和耐受性，人们研究了替代给药策略。本研究的目的是评估卡马西平经鼻内（IN）和静脉注射途径给药于小鼠后的药代动力学，并研究药物是否可能从鼻子直接转运至大脑。两种给药途径后在所有基质中获得的相似药代动力学特征表明，经鼻内给药后，卡马西平迅速且广泛地进入血液循环，主要通过体循环到达大脑。然而，与静脉注射后大脑均匀分布模式相比，经鼻内滴注后卡马西平在脑区的生物分布不均匀，在嗅球和额叶皮质中浓度较高，这强烈表明卡马西平存在从鼻子直接转运至大脑的情况。因此，经鼻内给药似乎是一种合适且有前景的替代途径，不仅适用于卡马西平的长期使用，也适用于紧急情况。
