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

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

SUBMITTER: Dias BB 

PROVIDER: S-EPMC11015084 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature