Pharmacokinetics,efficacy,and safety of a novel aripiprazole microsphere-based A novel long-acting injectable microsphere formulation of aripiprazole for schizophrenia:a multicenter,randomized controlled trial
LI An-ning
CUI Yi-min
JIN Sheng-chun
SHANG De-wei
GUO Jian-xiong
LIN Hua-li
ZHANG Ming
WEI Bo
WAN Feng
TAN Yun-long
WANG Li-li
ZHOU Jian-chu
LIU Ping
FAN Lian-lian
SUN Ju-shui
CHEN Bin
WANG Gang
Abstract：Objective:The aripiprazole microsphere-based long-acting injectable(LAI)formulation aims to enhance bioavailability and reduce total dose administered compared to traditional microcrystalline-based formulations.This study aims to evaluate the pharmacokinetic profiles and the bioequivalence between two formulations,in addition to assess the efficacy and safety of the microsphere-based formulations in patients with stable schizophrenia.Methods:A multicenter,randomized,open-label trial that enrolled 260 patients with stable schizophrenia was conducted.The subjects were randomly assigned in a 2∶2∶1 ratio to receive either an injection of 350 mg microsphere formulation(MS 350 mg)or a reference formulation of 400 mg(AM 400 mg)every 4 weeks(total 5 injections),or an injection of 500 mg microsphere formulation every 6 weeks(MS 500 mg,total 4 injections).The primary objective was to evaluate steady-state bioequivalence(AUC0-d28)and the degree of fluctuations in plasma concentration.The efficacy was evaluated using the Positive and Negative Syndrome Scale(PANSS)score,and the safety outcomes evaluated included treatment-emergent adverse events(TEAEs)and adverse drug reactions(ADRs).Results:The MS 350 mg formulation was bioequivalent to the AM 400 mg formulation.Both groups showed significant reduction in the PANSS score from baseline at week 12,20,and 24 after the first injection,with no significant difference between groups.The degree of fluctuation in plasma concentration were lower in the MS 350 mg group,which suggested a more stable drug exposure profile.The incidence of TEAEs and ADRs was lower in the MS 350 mg(75.7％vs 54.4％;83.5％vs 62.1％).Conclusion:The microsphere-based formulation demonstrated bioequivalence to the reference microcrystalline-based formulation,with sustained symptom improvement,lower plasma fluctuation,and a better safety profile.These findings supported the microsphere-based formulation as a viable choice for long-term schizophrenia management.
Keywords：aripiprazole microspherelong-acting injectable formulationpharmacokineticsefficacysafetydegree of fluctuation
Publication Date：2025-08-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：10( 1637-1646 )