Quetiapine Pharmacokinetic/Pharmacodynamic Modeling after Lipid Core Nanocapsules Administration to Schizophrenia Phenotyped Rats

Viewing to explore the pharmacokinetic (PK) and pharmacodynamic (PD) components of variability in schizophrenia response to treatment, a PK/PD model of cortical dopamine levels (CDL) after quetiapine lipid core nanocapsules¹ (QLNC) and quetiapine solution (FQ) administration to schizophrenia phenotyped rats (SPR) was developed. Quetiapine PK and PD after single i.v. bolus dose of 5 mg/kg of QLNC and FQ was investigated in plasma and brain, using microdialysis, of naïve and SPR (UFRGS/CEUA #31001). A semi-mechanistic PK model was linked to an indirect response PD model² to describe changes in CDL. Schizophrenia status increased EC50 about three times (naïve: 1.75 ng/mL; SPR: 4.97 ng/mL) reducing drug pharmacological sensitivity in SPR after the administration of FQ. QLNC formulation did not cause alterations in PD parameters; however, the increase in CDL of SPR after QLNC dosing highlights that the PK component of schizophrenia treatment variability can be overcome by this nanoformulation.