Population Pharmacokinetics for Switching From Oral or Long-Acting Injectable Risperidone to RYKINDO® (Risperidone) for Extended-Release Injectable Suspension, a Novel Long-Acting Injectable, in Patients With Schizophrenia

This work was sponsored by Shandong Luye Pharmaceutical Co., Ltd. RYKINDO® is a novel, long-acting injectable risperidone formulation administered biweekly (Q2W) through intramuscular gluteal injection for the treatment of schizophrenia in adult patients. This model-based analysis aimed to establish an approach to switch from RISPERDAL CONSTA® (RC; 25 mg Q2W) or RISPERDAL® (2 mg/day) to RYKINDO (25 mg Q2W) in adult patients with schizophrenia. Population pharmacokinetic (PK) models for RYKINDO and RC were developed based on data from phase 1 studies utilizing a non-linear mixed effects method; the RISPERDAL model used was developed by Vermeulen et al. Each simulation comprised 1000 virtual patients. Different simulations were conducted for distinct therapy-switching scenarios. The PK profiles of RYKINDO and RC were well represented by a one-compartment model with an immediate drug release followed by 2 delayed releases. RYKINDO showed a faster drug release (Cmax ~2.5 weeks) than RC (Cmax ~4.5 weeks). As such, switching from RC to RYKINDO requires administration of the first RYKINDO injection within 4-5 weeks after the last RC injection. For patients taking RISPERDAL, introducing RYKINDO coadministered with RISPERDAL once daily (QD) for 1 week can achieve comparable or superior exposure of the active moiety compared with 3-week coadministration of RISPERDAL QD required for the introduction of RC. While, after the first RYKINDO injection without continuing RISPERDAL resulted in lower exposure vs RC in the second week after the last oral dose, exposure was 25% higher than the lowest exposure of RC. This established approach provides guidance to physicians to initiate RYKINDO therapy in adult patients with schizophrenia.