Population Pharmacokinetic–Based Strategies for Switching Patients with Schizophrenia Between Long-Acting Injectable Formulations of Risperidone: R064766 or RBP-7000 to TV-46000

Document Type

Article

Publication Title

Neurology and Therapy

Abstract

Introduction: This analysis used pharmacokinetic (PK) modeling to characterize dosing conversions and switching strategies from R064766, a once-every-2-weeks, intramuscular long-acting injectable antipsychotic (LAI) formulation of risperidone microspheres, and RBP-7000, a subcutaneous (sc) LAI formulation of risperidone administered in the abdomen once monthly (q1m), to TV-46000, a q1m or once-every-2-months (q2m) sc LAI formulation of risperidone. Methods: Total active moiety (TAM; risperidone + 9-OH risperidone) concentration–time profiles were simulated on the basis of published population PK models with virtual populations of 5000 patients. Simulations were performed to predict TAM exposures when switching to TV-46000 q1m and q2m 2–6 weeks after the last steady-state R064766 injection and 4 weeks after the last dose of RBP-7000. Results: Comparable doses of oral risperidone, TV-46000, R064766, and RBP-7000 were identified. Initiating TV-46000 4–6 weeks after the last dose of R064766 resulted in similar trends for maximal (Cmax) and minimal (Cmin) plasma concentration ratios after the first injection for all TV-46000 doses and durations (q1m, q2m) compared with R064766 at steady state. Initiating TV-46000 q1m 4 weeks after the last dose of RBP-7000 resulted in slightly higher, but generally comparable, average plasma concentrations, Cmax, and Cmin at first dose and at steady state for TV-46000 compared with RBP-7000; Cmin of TV-46000 q2m and RBP-7000 were also comparable. Similar trends in plasma concentrations were observed for both back-of-the-upper-arm and abdominal administration when switching from R064766 and RBP-7000 to TV-46000. Conclusion: These simulations revealed switching to TV-46000 4–6 weeks after the last dose of R064766 and 4 weeks after the last dose of RBP-7000 provided generally comparable PK exposures at first dose and steady state of TV-46000. Clinician discretion will determine which switching strategy is most appropriate in context based on factors such as patient preference, scheduling convenience, and concerns about tolerability.

First Page

2647

Last Page

2667

DOI

10.1007/s40120-025-00840-9

Publication Date

12-1-2025

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