【摘要】 目的:与传统的微晶剂型相比，基于微球技术的阿立哌唑长效注射剂（long-acting injectable formulation,LAI）旨在提高生物利用度并减少总剂量。本研究旨在评估2种剂型的药动学特征和生物等效性，并评估阿立哌唑微球长效制剂对稳定期精神分裂症患者的疗效和安全性。方法:本研究为一项多中心随机开放标签临床试验，共纳入260例稳定期精神分裂症患者。受试者按2∶2∶1的比例随机分配，分别每4周注射1次微球制剂350 mg（MS 350 mg）或对照制剂400 mg（AM 400 mg）共5次注射;或每6周注射1次500 mg微球制剂（MS 500 mg）共4次注射。主要目的是评估稳态生物等效性(AUC_0-d28)和血浆浓度的波动程度。采用阳性和阴性症状量表（positive and negative symptom scale,PANSS）评分评估疗效，安全性结果评估包括治疗出现的不良事件（treatment-emergent adverse events,TEAEs）和药物不良反应（adverse drug reactions,ADRs）。结果:MS 350 mg制剂与AM 400 mg制剂具有生物等效性。两组在第1次注射后第12周、第20周和第24周的PANSS评分均较基线显著降低，组间无显著差异。MS 350 mg组血药浓度波动程度较低，表明其药物暴露谱更为稳定。MS 350 mg组的TEAEs（75.7%vs 54.4%）及ADRs（83.5%vs 62.1%）发生率均低于AM 400 mg组。结论:微球制剂与微晶制剂具有生物等效性，可持续改善患者症状，血浆波动更小且安全性更优。这些研究结果支持微球制剂作为精神分裂症长期治疗的可行方案。更多还原

【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( AUC_0-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 MS350 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.更多还原