A review of clinical applications of pharmacokinetic simulations for a 2-month long-acting injectable formulation of aripiprazole

Abstract

Aripiprazole 2-month ready-to-use (Ari 2MRTU) is a long-acting injectable antipsychotic that was approved for use in Europe in March 2024, for the maintenance treatment of schizophrenia in adult patients stabilized with aripiprazole; it is administered via gluteal intramuscular injection once every two months. This review examines population pharmacokinetic model-based simulations relevant to the use of Ari 2MRTU in Europe, accompanied by expert commentary that contextualizes the simulations and highlights the potential implications of the availability of Ari 2MRTU for patients, caregivers, and clinicians. Various simulations conducted across 8 weeks (representing the first dosing interval), or 32 weeks (representing maintenance dosing) demonstrated an aripiprazole exposure profile for Ari 2MRTU that was similar to aripiprazole once-monthly (AOM), but with an extended dosing interval. In treatment initiation scenarios consistent with the European label, therapeutic levels of aripiprazole (i.e. ≥95 ng/mL) were maintained when transitioning from either AOM or oral aripiprazole, including with a two-injection start regimen with no requirement for 14 days of oral aripiprazole supplementation. Therapeutic levels of aripiprazole were also observed for treatment maintenance scenarios, except when dosing of Ari 2MRTU was delayed by 8 weeks. The availability of Ari 2MRTU extends the range of options for the maintenance treatment of schizophrenia in Europe. Ari 2MRTU may provide adherence benefits due to its extended dosing interval and the option to initiate treatment using a two-injection start regimen, which does not require 14 days of overlapping oral supplementation.

Keywords: Aripiprazole; injections, intramuscular; pharmacokinetics; schizophrenia.