Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD, USA.
Schizophr Res. 2013 Oct;150(1):281-8. doi: 10.1016/j.schres.2013.06.041. Epub 2013 Jul 23.
This 24-week, open-label, Phase Ib, parallel-arm, multiple-dose trial assessed the pharmacokinetics, safety and tolerability of a once-monthly injection of aripiprazole (aripiprazole once-monthly) in 41 subjects with schizophrenia. The objective was to determine if aripiprazole plasma concentrations (at doses of 200, 300 and 400mg) were within the therapeutic range observed for the oral tablet (10-30 mg). Completion rates were 36.4% (n=4/11), 50.0% (n=8/16) and 71.4% (n=10/14) for the 200mg, 300 mg and 400mg groups, respectively. Patients were stabilized on oral aripiprazole (10mg/day) before the first injection and received oral aripiprazole (10mg/day) concomitantly with the first dose of aripiprazole once-monthly for 14 days. Administration of aripiprazole once-monthly at doses of 300 and 400mg provided sustained mean aripiprazole plasma concentrations comparable with the concentration range observed following multiple consecutive daily doses of oral aripiprazole. In contrast, plasma concentrations following administration of aripiprazole once-monthly at a dose of 200mg were below the therapeutic range and pharmacokinetic parameters were not proportional to the administered dose compared with the 300 mg and 400mg doses. Treatment with aripiprazole once-monthly, at any dose, did not result in any clinically meaningful changes from baseline in extrapyramidal symptom scales, clinical laboratory tests, vital signs, or electrocardiogram parameters. The most common treatment-emergent adverse events were vomiting (13.3%, 300 mg; 14.3%, 400mg), injection site pain (28.6%, 400mg), upper respiratory tract infection (10%, 200mg; 6.7% 300 mg; 14.3%, 400mg) and tremor (6.7%, 300 mg; 21.4%, 400mg). In conclusion, aripiprazole once-monthly at doses of 300 and 400mg is a viable formulation for treatment of adults with schizophrenia.
这项 24 周、开放性、Ib 期、平行臂、多剂量试验评估了每月一次注射阿立哌唑（阿立哌唑每月一次）在 41 例精神分裂症患者中的药代动力学、安全性和耐受性。目的是确定阿立哌唑的血浆浓度（在 200、300 和 400mg 剂量下）是否在口服片剂（10-30mg）观察到的治疗范围内。200mg、300mg 和 400mg 组的完成率分别为 36.4%（n=4/11）、50.0%（n=8/16）和 71.4%（n=10/14）。在第一次注射前，患者在口服阿立哌唑（10mg/天）稳定后，同时接受口服阿立哌唑（10mg/天）和阿立哌唑每月一次的第一次剂量共 14 天。在 300mg 和 400mg 剂量下，每月一次给予阿立哌唑可提供持续的平均阿立哌唑血浆浓度，与多次连续每日口服阿立哌唑后的浓度范围相当。相比之下，200mg 剂量下给予阿立哌唑每月一次的血浆浓度低于治疗范围，与 300mg 和 400mg 剂量相比，药代动力学参数与给药剂量不成比例。任何剂量的阿立哌唑每月一次治疗均不会导致锥体外系症状量表、临床实验室检查、生命体征或心电图参数与基线相比出现任何有临床意义的变化。最常见的治疗后出现的不良事件是呕吐（13.3%，300mg；14.3%，400mg）、注射部位疼痛（28.6%，400mg）、上呼吸道感染（10%，200mg；6.7%，300mg；14.3%，400mg）和震颤（6.7%，300mg；21.4%，400mg）。总之，阿立哌唑每月一次的 300mg 和 400mg 剂量是治疗成人精神分裂症的可行制剂。
