We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats.
- Authors
Dias, Bruna Bernar; Carreño, Fernando; Helfer, Victória Etges; Olivo, Laura Ben; Staudt, Keli Jaqueline; Paese, Karina; Barreto, Fabiano; Meyer, Fabíola Schons; Herrmann, Ana Paula; Guterres, Sílvia Stanisçuaski; Rates, Stela Maris Kuze; de Araújo, Bibiana Verlindo; Trocóniz, Iñaki F.; Dalla Costa, Teresa
- Abstract
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 semimechanistic 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 concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. 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 neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.
- Subjects
NANOCAPSULES; PHARMACOKINETICS; QUETIAPINE; DRUG therapy; PREFRONTAL cortex; DOPAMINE receptors; DOPAMINE; ARIPIPRAZOLE
- Publication
CPT: Pharmacometrics & Systems Pharmacology, 2024, Vol 13, Issue 4, p638
- ISSN
2163-8306
- Publication type
Article
- DOI
10.1002/psp4.13107