Selim Sally, Riesenberg Robert, Cassella James, Kunta Jeevan, Hellriegel Edward, Smith Mark A, Vinks Alexander A, Rabinovich-Guilatt Laura
Clinical Development, Teva Pharmaceutical Industries, Frazer, PA, USA.
Atlanta Center for Medical Research, Atlanta, GA, USA.
J Clin Pharmacol. 2017 Oct;57(10):1244-1257. doi: 10.1002/jcph.932. Epub 2017 May 16.
This multisite open-label study sought to characterize the pharmacokinetics and safety of a single dose of inhaled loxapine in children and adolescents. Loxapine powder for oral inhalation was administered via a single-use handheld drug device to children and adolescents (aged 10-17 years) with any condition warranting chronic antipsychotic use. Patients were dosed according to body weight and cohort (<50 kg [n = 15], 2.5 or 5 mg; ≥50 kg [n = 15], 5 or 10 mg); the first 6 patients (cohort 1) enrolled in each weight group received the lower dose. Patients were enrolled in the higher-dose group (cohort 2) after an interim pharmacokinetic and safety analysis of data from cohort 1. Blood samples were collected for 48 hours after dosing to determine the pharmacokinetic profile of loxapine and its metabolites. Safety was assessed using adverse event (AE), laboratory value, physical/neurologic examination, vital sign, electrocardiogram, suicidality, and extrapyramidal symptom assessment. Thirty patients were enrolled and evaluable for pharmacokinetics. Loxapine plasma concentrations peaked by 2 to 5 minutes in most patients; systemic exposure increased with dose in both weight subgroups. Loxapine terminal elimination half-life was ∼13 to 17 hours. The most common AEs were sedation and dysgeusia. Sedation was severe in 1 patient in the <50-kg group (2.5-mg dose) and 1 patient in the ≥50-kg group (5-mg dose). No AEs indicative of bronchospasm or other serious AEs were reported. Inhaled loxapine was rapidly absorbed and generally well tolerated in pediatric patients; no new safety signals were observed.
这项多中心开放标签研究旨在描述儿童和青少年单次吸入洛沙平的药代动力学和安全性。口服吸入用洛沙平粉末通过一次性手持式给药装置给予患有任何需要长期使用抗精神病药物治疗疾病的儿童和青少年（10 - 17岁）。患者根据体重和队列分组给药（<50 kg [n = 15]，2.5或5 mg；≥50 kg [n = 15]，5或10 mg）；每个体重组入组的前6名患者（队列1）接受较低剂量。在对队列1的数据进行中期药代动力学和安全性分析后，患者被纳入高剂量组（队列2）。给药后48小时采集血样以确定洛沙平及其代谢物的药代动力学特征。使用不良事件（AE）、实验室检查值、体格/神经学检查、生命体征、心电图、自杀倾向和锥体外系症状评估来评估安全性。30名患者入组并可进行药代动力学评估。大多数患者的洛沙平血浆浓度在2至5分钟达到峰值；两个体重亚组的全身暴露均随剂量增加。洛沙平的终末消除半衰期约为13至17小时。最常见的不良事件是镇静和味觉障碍。<50 kg组（2.5 mg剂量）和≥50 kg组（5 mg剂量）各有1名患者出现严重镇静。未报告提示支气管痉挛或其他严重不良事件的不良事件。吸入洛沙平在儿科患者中吸收迅速且总体耐受性良好；未观察到新的安全信号。
