Poster
146
(#146) Pharmacokinetic-Pharmacodynamic Modeling and of Switching From Aripiprazole Monohydrate to TV-46000, a Long-Acting Subcutaneous Risperidone, in a Virtual Population of Patients With Schizophrenia
Psych Congress 2025
Abstract: Background: TV-46000 is a long-acting injectable (LAI) subcutaneous risperidone antipsychotic administered once monthly (q1m) or every 2 months (q2m) for schizophrenia. Transitioning from aripiprazole once monthly (AOM), a partial dopamine D2-receptor (D2R) agonist (allows 25% D2R activity), to TV-46000, a D2R antagonist (blocks receptor activity), requires consideration of pharmacodynamic differences. Aripiprazole has higher D2-binding affinity and requires high receptor occupancy (D2RO) for antagonism, while risperidone exerts antagonism at any D2RO. This study used population pharmacokinetic-pharmacodynamic modeling to simulate AOM to TV-46000 switching and assess D2RO and antagonism.
Methods: Population pharmacokinetic models were used to simulate plasma concentrations, D2RO, and antagonism during a switch from AOM 400 mg to TV-46000 125 mg q1m or 250 mg q2m, 28 days after the last AOM dose among 500 virtual participants. Competitive binding models evaluated D2RO and antagonism over time.
Results: AOM pre-switch D2RO was 91%, with 68% antagonism. After first TV-46000 q1m dose, D2RO was 71% for AOM/19% for TV-46000 (total=90%); antagonism was 53%/19%, respectively (total=73%). After first TV-46000 q2m dose, D2RO was 62% for AOM/27% for TV-46000 (total=89%); antagonism was 47%/27%, respectively (total=74%). As TV-46000 approached steady-state (after 3 doses), antagonism was 14%-29% (AOM) and 49%-64% (TV-46000). AOM's contribution to total antagonism was 5% after 5 (q2m) or 9 (q1m) TV-46000 doses.
Conclusions: Simulations demonstrated that switching from AOM 400 mg to TV-46000 125 mg q1m or 250 mg q2m maintained total antagonism despite slightly lower D2RO. Clinicians should consider patient preference and tolerability when switching LAIs.
Short Description: This study used pharmacokinetic-pharmacodynamic modeling to simulate switching from aripiprazole once monthly 400 mg to TV-46000, a long-acting risperidone formulation for schizophrenia, 125 mg once monthly or 250 mg once every 2 months. Simulations showed that TV-46000 maintained comparable dopamine D2-receptor occupancy and antagonism despite pharmacologic differences. Results support that switching between the 2 formulations preserved D2-receptor antagonism, however clinical decisions should be guided by patient preference, convenience, and tolerability.
Name of Sponsoring Organization(s): Teva Branded Pharmaceutical Products R&D LLC
Methods: Population pharmacokinetic models were used to simulate plasma concentrations, D2RO, and antagonism during a switch from AOM 400 mg to TV-46000 125 mg q1m or 250 mg q2m, 28 days after the last AOM dose among 500 virtual participants. Competitive binding models evaluated D2RO and antagonism over time.
Results: AOM pre-switch D2RO was 91%, with 68% antagonism. After first TV-46000 q1m dose, D2RO was 71% for AOM/19% for TV-46000 (total=90%); antagonism was 53%/19%, respectively (total=73%). After first TV-46000 q2m dose, D2RO was 62% for AOM/27% for TV-46000 (total=89%); antagonism was 47%/27%, respectively (total=74%). As TV-46000 approached steady-state (after 3 doses), antagonism was 14%-29% (AOM) and 49%-64% (TV-46000). AOM's contribution to total antagonism was 5% after 5 (q2m) or 9 (q1m) TV-46000 doses.
Conclusions: Simulations demonstrated that switching from AOM 400 mg to TV-46000 125 mg q1m or 250 mg q2m maintained total antagonism despite slightly lower D2RO. Clinicians should consider patient preference and tolerability when switching LAIs.
Short Description: This study used pharmacokinetic-pharmacodynamic modeling to simulate switching from aripiprazole once monthly 400 mg to TV-46000, a long-acting risperidone formulation for schizophrenia, 125 mg once monthly or 250 mg once every 2 months. Simulations showed that TV-46000 maintained comparable dopamine D2-receptor occupancy and antagonism despite pharmacologic differences. Results support that switching between the 2 formulations preserved D2-receptor antagonism, however clinical decisions should be guided by patient preference, convenience, and tolerability.
Name of Sponsoring Organization(s): Teva Branded Pharmaceutical Products R&D LLC
