Abstract

Background

The single-injection start regimen for aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia requires a single intramuscular injection in the gluteal or deltoid site and 14 days of concurrent oral therapy. A simplified, single-day regimen of two injections at separate gluteal and/or deltoid injection sites, together with a single 20-mg dose of oral aripiprazole on the 1st day, was assessed.

Patients and methods

A previously developed population-pharmacokinetic (popPK) model for characterizing aripiprazole PK following oral administration and gluteal intramuscular depot injection was expanded to include deltoid injection. Simulations were conducted to assess PK profiles following various (including two-injection) start regimens. Postmarketing data on patients who received higher-than-recommended AOM doses were used to assess overall safety/tolerability.

Results

The two-injection start regimen with a single concurrent oral dose displayed a comparable PK profile to the single-injection start regimen with concurrent 14-day oral administration in simulations. The safety assessment indicated the two-injection start regimen was unlikely to be associated with safety concerns beyond those expected with a single-injection start regimen.

Conclusion

These data support use of the two-injection start regimen in clinical practice to reduce reliance on daily oral administration and optimize the therapeutic benefits of AOM 400 in patients with schizophrenia.

中文翻译：

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精神分裂症患者每月一次使用阿立哌唑的替代起始方案：从臀肌和/或三角肌肌内注射开始的单天两次注射的群体药代动力学分析

摘要

背景

在精神分裂症患者中，阿立哌唑每月一次 400 mg (AOM 400) 的单次注射开始方案需要在臀部或三角肌部位进行单次肌肉注射和 14 天的同时口服治疗。评估了在不同的臀部和/或三角肌注射部位进行两次注射的简化单日方案，并在第一天口服单剂 20 毫克阿立哌唑。

患者和方法

先前开发的用于表征口服给药和臀肌内长效注射后阿立哌唑 PK 的群体药代动力学 (popPK) 模型已扩展为包括三角肌注射。进行模拟以评估各种（包括两次注射）开始方案后的 PK 曲线。接受高于推荐 AOM 剂量的患者的上市后数据用于评估总体安全性/耐受性。

结果

在模拟中，单次同时口服剂量的两次注射开始方案显示出与单次注射开始方案和同时口服给药 14 天的相当的 PK 曲线。安全性评估表明，两次注射开始方案不太可能与单次注射开始方案预期之外的安全问题相关。

结论

这些数据支持在临床实践中使用两次注射开始方案，以减少对每日口服给药的依赖并优化 AOM 400 在精神分裂症患者中的治疗益处。