AbbVie, Madison, New Jersey, USA.
Atlanta Center for Medical Research, Atlanta, Georgia, USA.
J Child Adolesc Psychopharmacol. 2022 Oct;32(8):434-443. doi: 10.1089/cap.2021.0139.
Cariprazine is a dopamine D-preferring D/D and serotonin 5-HT receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This sequential-cohort, dose-escalation study was the first to evaluate the pharmacokinetic, safety, and tolerability profile of cariprazine and its two major active metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR), in pediatric patients with schizophrenia or bipolar I disorder. This phase I open-label study enrolled patients with schizophrenia (13-17 years of age) or bipolar I disorder (10-17 years of age). Patients met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia or bipolar I disorder and had Positive and Negative Syndrome Scale (PANSS) total scores ≥70 or Young Mania Rating Scale (YMRS) total scores ≥20. Patients were assigned to one of four treatment groups to receive 6 weeks of cariprazine treatment through slow titration to 1.5, 3, or 4.5 mg/d or fast titration to 4.5 mg/d. Pharmacokinetics, adverse events (AEs), and various safety parameters were analyzed. Efficacy was evaluated as an exploratory outcome. A total of 50 participants were enrolled. Based on mean trough levels, steady state appeared to be reached within 1-2 weeks for cariprazine and DCAR and within 4-5 weeks for DDCAR. Systemic exposure of cariprazine, DCAR, and DDCAR generally increased approximately in proportion to the increases in dose from 1.5 to 4.5 mg/d. The most frequent treatment-related, treatment-emergent AEs included sedation, parkinsonism, tremor, dystonia, and blurred vision. Improvements from baseline on the PANSS and YMRS were observed throughout treatment. In this first investigation of cariprazine in a pediatric population with schizophrenia or bipolar disorder, pharmacokinetic parameters were consistent with those observed in adults. Cariprazine appeared to be safe and tolerable in children and adolescents.
卡利拉嗪是一种多巴胺 D 受体优先 D/D 和 5-羟色胺 5-HT 受体部分激动剂，已被批准用于治疗成人精神分裂症和双相 I 障碍相关的躁狂/混合或抑郁发作。这项序贯队列、剂量递增研究是首次评估卡利拉嗪及其两种主要活性代谢物去甲卡利拉嗪 (DCAR) 和双去甲卡利拉嗪 (DDCAR) 在精神分裂症或双相 I 障碍儿科患者中的药代动力学、安全性和耐受性特征。这项 I 期开放标签研究纳入了精神分裂症 (13-17 岁) 或双相 I 障碍 (10-17 岁) 的患者。患者符合精神分裂症或双相 I 障碍的《精神疾病诊断与统计手册》第五版 (DSM-5) 标准，阳性和阴性综合征量表 (PANSS) 总分≥70 分或 Young Mania Rating Scale (YMRS) 总分≥20 分。患者被分配到四个治疗组中的一个，接受 6 周的卡利拉嗪治疗，通过缓慢滴定至 1.5、3 或 4.5mg/d 或快速滴定至 4.5mg/d。对药代动力学、不良事件 (AE) 和各种安全性参数进行了分析。疗效作为探索性结果进行评估。共纳入 50 名参与者。基于平均谷浓度，卡利拉嗪和 DCAR 约在 1-2 周内、DDCAR 约在 4-5 周内达到稳态。卡利拉嗪、DCAR 和 DDCAR 的全身暴露量一般与从 1.5 至 4.5mg/d 剂量增加成比例增加。最常见的与治疗相关的、治疗出现的 AE 包括镇静、帕金森病、震颤、肌张力障碍和视力模糊。在整个治疗过程中，PANSS 和 YMRS 均从基线改善。在这项对精神分裂症或双相障碍儿科人群的卡利拉嗪首次研究中，药代动力学参数与成人观察到的一致。卡利拉嗪在儿童和青少年中似乎是安全且耐受良好的。
