Findling Robert L, Robb Adelaide S, DelBello Melissa, Huss Michael, McNamara Nora, Sarkis Elias, Scheffer Russell, Poulsen Lis H, Chen Grace, Lemming Ole Michael, Areberg Johan, Auby Philippe
1 Department of Psychiatry and Behavioral Sciences, Kennedy Krieger Institute and Johns Hopkins University , Baltimore, Maryland.
2 Department of Psychology and Behavioral Health, Children's National Health Systems , Washington, District of Columbia.
J Child Adolesc Psychopharmacol. 2017 Aug;27(6):526-534. doi: 10.1089/cap.2016.0155. Epub 2017 Mar 23.
The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials.
This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing.
Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults.
The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.
本研究的主要目的是评估单剂量和多剂量伏硫西汀在患有抑郁或焦虑症的儿童和青少年中的药代动力学（PK）及耐受性，并为儿科临床试验的合适给药方案提供支持性信息。
这项前瞻性、开放标签、多国、多中心、多剂量试验纳入了48例患者（儿童和青少年；比例为1:1），分为8个队列（4个青少年队列和4个儿童队列），每个队列包括6例患者。每个年龄组的队列被分配接受四种给药方案之一：伏硫西汀5、10、15或20毫克每日一次，共14天。总治疗期持续14 - 20天，高剂量队列的患者在2 - 6天内递增剂量。在给药的第一天和最后一天采集用于PK分析的血浆样本。
在儿童和青少年中，分别有62%和92%患有抑郁症，58%和33%患有焦虑症。50%的儿童和38%的青少年存在共病注意力缺陷/多动障碍（ADHD）。在目标剂量每日一次给药14天后，伏硫西汀浓度的PK在两个年龄组中通常与剂量成比例。通过最大血浆浓度和0至24小时血浆浓度 - 时间曲线下面积评估的暴露量，青少年比儿童低30% - 40%。性别、身高或ADHD诊断与PK参数之间无显著关系。大多数不良事件严重程度为轻度，与成人中所见一致。
结果表明，所评估的伏硫西汀剂量（5 - 20毫克每日一次；已批准用于成人治疗）和所用的递增给药方案适用于儿科疗效和安全性试验。
