Hard Marjie L, Wehr Angela, von Moltke Lisa, Du Yangchun, Farwick Sarah, Walling David P, Sonnenberg John
Alkermes, Inc., Waltham, MA, USA.
Uptown Research Institute, Chicago, IL, USA.
Ther Adv Psychopharmacol. 2019 Jul 2;9:2045125319859964. doi: 10.1177/2045125319859964. eCollection 2019.
Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia in adults, can be started with either 21 days of daily oral aripiprazole supplementation or a 1-day initiation regimen consisting of a single injection of a NanoCrystal Dispersion formulation of AL (AL) and a single dose of 30 mg oral aripiprazole. This phase I study assessed the pharmacokinetics and safety of deltoid gluteal AL injections.
Patients with schizophrenia or schizoaffective disorder ( = 47) were randomized 1:1 to receive a single intramuscular dose of AL in the deltoid or gluteal muscle. Plasma samples were collected over 85 days to measure AL concentration by injection site. Relative aripiprazole bioavailability for deltoid gluteal injection was assessed based on area under the curve (AUC and AUC) and maximum concentration (C) values. Adverse events were monitored throughout the study.
Plasma aripiprazole concentrations after a single AL injection were comparable between deltoid and gluteal administration. Mean maximum plasma aripiprazole concentrations were 196.1 ng/ml (deltoid) and 175.0 ng/ml (gluteal). Exposure to aripiprazole was similar, with mean AUC values of 6591 day × ng/ml for deltoid and 6437 day × ng/ml for gluteal. Aripiprazole bioavailability was not significantly different between injection sites. AL administration in the deltoid or gluteal muscle was well tolerated, with similar safety profiles at both sites.
AL demonstrated similar exposure and safety profiles between the two administration sites, suggesting that AL can be given in either the gluteal or the deltoid muscles as a component of the 1-day initiation regimen for AL.
阿立哌唑长效注射剂（AL）是一种用于治疗成人精神分裂症的长效注射用抗精神病药物，可通过每日口服阿立哌唑补充剂21天或由单次注射AL的纳米晶体分散制剂（AL）和单剂量30mg口服阿立哌唑组成的1天起始方案开始使用。这项I期研究评估了三角肌和臀肌注射AL的药代动力学和安全性。
将47例精神分裂症或分裂情感性障碍患者按1:1随机分组，分别接受三角肌或臀肌单次肌内注射AL。在85天内采集血浆样本，以按注射部位测量AL浓度。基于曲线下面积（AUC和AUC）和最大浓度（C）值评估三角肌与臀肌注射阿立哌唑的相对生物利用度。在整个研究过程中监测不良事件。
单次注射AL后，三角肌和臀肌给药后的血浆阿立哌唑浓度相当。平均最大血浆阿立哌唑浓度分别为196.1ng/ml（三角肌）和175.0ng/ml（臀肌）。阿立哌唑的暴露情况相似，三角肌的平均AUC值为6591天×ng/ml，臀肌为6437天×ng/ml。注射部位之间阿立哌唑的生物利用度无显著差异。三角肌或臀肌注射AL耐受性良好，两个部位的安全性相似。
AL在两个给药部位显示出相似的暴露和安全性，表明AL可作为AL 1天起始方案的一部分，在臀肌或三角肌注射。
