Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats

• Autor(a) principal: Dias, Bruna Bernar
• Data de Publicação: 2024
• Outros Autores: Carreño, Fernando, Helfer, Victória Etges, Olivo, Laura Ben, Staudt, Keli Jaqueline, Paese, Karina, Barreto, Fabiano, Meyer, Fabiola Schons, Herrmann, Ana Paula, Guterres, Silvia Stanisçuaski, Rates, Stela Maris Kuze, Araújo, Bibiana Verlindo de, Trocóniz, Iñaki, Dalla Costa, Teresa Cristina Tavares
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/280161
• topic: Tratamento farmacológico; Transtornos mentais; Esquizofrenia; Nanopartículas

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration–effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semi-mechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular con-centrations determined by intracerebral microdialysis. Different structural mod-els were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool com-partment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelop-mental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.