Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU): review of its possible role in schizophrenia therapy

Baune, Bernhard T.

doi:10.1080/03007995.2023.2287612

Cited by 2 publications

(1 citation statement)

References 78 publications

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“…For SZ patients undergoing long-term treatment, effective and well-tolerated pharmacological therapy is key. Aripiprazole is a third-generation atypical antipsychotic indicated for SZ that is one of the most well tolerated and with the least discontinuation in patients [20,21]. It acts as a partial agonist of the D2 dopaminergic receptor and a full antagonist of the 5-HT 2A serotoninergic receptor [22].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model

Adraoui,

Hettak,

Viardot

et al. 2024

IJMS

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The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms and do not significantly modify SZ neurobiology. This has raised the question of the robustness and translational value of methods employed during drug development. Electroencephalography (EEG)-based measures like evoked and spontaneous gamma oscillations are considered robust translational biomarkers as they can be recorded in both patients and animal models to probe a key mechanism underlying all SZ symptoms: the excitation/inhibition imbalance mediated by N-methyl-D-aspartate receptor (NMDAr) hypofunction. Understanding the effects of commercialized atypical antipsychotics on such measures could therefore contribute to developing better therapies for SZ. Yet, the effects of such drugs on these EEG readouts are unknown. Here, we studied the effect of the atypical antipsychotic aripiprazole on the gamma-band auditory steady-state response (ASSR), spontaneous gamma oscillations and behavioral features in a SZ rat model induced by the NMDAr antagonist MK-801. Interestingly, we found that aripiprazole could not normalize MK-801-induced abnormalities in ASSR, spontaneous gamma oscillations or social interaction while it still improved MK-801-induced hyperactivity. Suggesting that aripiprazole is unable to normalize electrophysiological features underlying SZ symptoms, our results might explain aripiprazole’s inefficacy towards the social interaction deficit in our model but also its limited efficacy against social symptoms in patients.

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Section: Introductionmentioning

confidence: 99%

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model

Adraoui,

Hettak,

Viardot

et al. 2024

IJMS

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Population Pharmacokinetics and Dosing Simulations for Aripiprazole 2‐Month Ready‐to‐Use Long‐Acting Injectable in Adult Patients With Schizophrenia or Bipolar I Disorder

Wang,

Harlin,

Larsen

et al. 2024

Clinical Pharm in Drug Dev

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A ready‐to‐use (RTU) long‐acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, available in 960 mg (Ari 2MRTU 960) or 720 mg doses, has been developed for the treatment of schizophrenia or bipolar I disorder. A previously developed and validated population pharmacokinetic model for characterizing aripiprazole plasma concentrations following administration of oral aripiprazole or aripiprazole once‐monthly (AOM) intramuscular injection was expanded to include the RTU LAI formulation of aripiprazole (Ari RTU LAI). Overall, 8899 aripiprazole pharmacokinetic samples from 1191 adults from 10 clinical trials were included in the final combined analysis data set. Aripiprazole plasma concentration‐time profiles were simulated for various Ari RTU LAI initiation and maintenance scenarios in 1000 virtual patients. Diagnostic plots demonstrated that the final population pharmacokinetic model, which incorporated data for oral aripiprazole, AOM, and Ari RTU LAI, adequately described aripiprazole concentrations following Ari RTU LAI administration. Absorption of Ari RTU LAI was modeled by a parallel zero‐order and lagged first‐order process. Simulations across multiple scenarios were performed to inform dosing recommendations, including various treatment initiation regimens for a 2‐monthly formulation of Ari RTU LAI in patients with or without prior stabilization on oral aripiprazole, and for patients switching from AOM. Additional simulations accounted for missed/delayed doses, cytochrome (CYP) 2D6 metabolizer status, and concomitant use of CYP2D6 or CYP3A4 inhibitors. Overall, simulations across a variety of scenarios demonstrated an Ari RTU LAI pharmacokinetic exposure profile that was comparable to AOM, with a longer dosing interval.

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Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU): review of its possible role in schizophrenia therapy

Cited by 2 publications

References 78 publications

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model

Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model

Population Pharmacokinetics and Dosing Simulations for Aripiprazole 2‐Month Ready‐to‐Use Long‐Acting Injectable in Adult Patients With Schizophrenia or Bipolar I Disorder

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