Population Pharmacokinetic-Based Strategies for Switching Patients with Schizophrenia Between Long-Acting Injectable...

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.

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.

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 (C_max) and minimal (C_min) 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, C_max, and C_min at first dose and at steady state for TV-46000 compared with RBP-7000; C_min 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.

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.