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. 2024 Jun;13(6):631-643.
doi: 10.1002/cpdd.1397. Epub 2024 Apr 11.

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

Yanlin Wang  1 , Matthew Harlin  1 , Frank Larsen  2 , Xiaofeng Wang  1 , Wansu Park  3 , Benjamin Rich  4 , Jogarao V Gobburu  5 , Arash Raoufinia  1
Affiliations

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

Yanlin Wang et al. Clin Pharmacol Drug Dev. 2024 Jun.

Abstract

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.

Keywords: 2‐month ready‐to‐use; aripiprazole; long‐acting injectable; population pharmacokinetics; simulations.

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References

    1. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067.
    1. Vieta E, Berk M, Schulze TG, et al. Bipolar disorders. Nat Rev Dis Primers. 2018;4:18008
    1. Kasper S, Lerman MN, McQuade RD, et al. Efficacy and safety of aripiprazole vs. haloperidol for long‐term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol. 2003;6(4):325‐337.
    1. Kramer M, Simpson G, Maciulis V, et al. Paliperidone extended‐release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double‐blind, placebo‐controlled study. J Clin Psychopharmacol. 2007;27(1):6‐14.
    1. Tohen M, Calabrese JR, Sachs GS, et al. Randomized, placebo‐controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry. 2006;163(2):247‐256.