Publicação
Pharmacokinetic evaluation of a non-steroidal anti-inflammatory drug after intranasal administration to mice
| Resumo: | The neuroinflammation process describes the extensive range of inflammatory and immunological responses of the central nervous system (CNS), referring to the activation of microglia and astrocytes. It occurs in several diseases associated with the CNS, such as neurodegenerative diseases and neuropsychiatric pathologies. It is characterized as a self-defense reaction which aims to eliminate potentially harmful stimuli and restore tissue integrity. However, when it exceeds physiological limits, neuroinflammation stops being neuroprotective and becomes neurodegenerative, a condition established when it lasts for a long period of time with nefarious effects on the CNS. In this way, the present work investigated the intranasal (IN) administration of a non-steroidal anti-inflammatory drug (NSAID). NSAIDs have been studied with the aim of acting on the inflammatory component of CNS diseases, but their chronic use is still quite limited due to their peripheral adverse effects. Due to this evidence, their IN administration is expected to be advantageous, mainly because it provides an opportunity to improve the access to the CNS and reduce peripheral exposure. The main objective of the proposed research project was to characterize the pharmacokinetic profile of a NSAID, piroxicam, after its IN and intravenous (IV) administration to CD-1 mice. Its quantification was performed using high-performance liquid chromatography with diode-array detection (HPLC-DAD), validated according to international standards, in different biological matrices (plasma, brain and lung). The results showed similar pharmacokinetic profiles for the two routes of administration in the different matrices. In plasma, drug exposure was slightly higher after IN dosing. Regarding the brain, it was found that the passage of piroxicam to the CNS is mainly through systemic circulation and, in the lungs, the IN route showed identical exposure to the IV route. Future pharmacokinetic studies with oral dosing are suggested, in order to compare and ascertain the potential of the IN route for piroxicam administration. |
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| Autores principais: | Santos, Mariana Nunes dos |
| Assunto: | non-steroidal anti-inflammatory drugs intranasal route pharmacokineticspharmacokinetics anti-inflamatórios não esteróides via intranasal farmacocinética |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | The neuroinflammation process describes the extensive range of inflammatory and immunological responses of the central nervous system (CNS), referring to the activation of microglia and astrocytes. It occurs in several diseases associated with the CNS, such as neurodegenerative diseases and neuropsychiatric pathologies. It is characterized as a self-defense reaction which aims to eliminate potentially harmful stimuli and restore tissue integrity. However, when it exceeds physiological limits, neuroinflammation stops being neuroprotective and becomes neurodegenerative, a condition established when it lasts for a long period of time with nefarious effects on the CNS. In this way, the present work investigated the intranasal (IN) administration of a non-steroidal anti-inflammatory drug (NSAID). NSAIDs have been studied with the aim of acting on the inflammatory component of CNS diseases, but their chronic use is still quite limited due to their peripheral adverse effects. Due to this evidence, their IN administration is expected to be advantageous, mainly because it provides an opportunity to improve the access to the CNS and reduce peripheral exposure. The main objective of the proposed research project was to characterize the pharmacokinetic profile of a NSAID, piroxicam, after its IN and intravenous (IV) administration to CD-1 mice. Its quantification was performed using high-performance liquid chromatography with diode-array detection (HPLC-DAD), validated according to international standards, in different biological matrices (plasma, brain and lung). The results showed similar pharmacokinetic profiles for the two routes of administration in the different matrices. In plasma, drug exposure was slightly higher after IN dosing. Regarding the brain, it was found that the passage of piroxicam to the CNS is mainly through systemic circulation and, in the lungs, the IN route showed identical exposure to the IV route. Future pharmacokinetic studies with oral dosing are suggested, in order to compare and ascertain the potential of the IN route for piroxicam administration. |
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