Konofal Eric, Zhao Wei, Laouénan Cédric, Lecendreux Michel, Kaguelidou Florentia, Benadjaoud Lila, Mentré France, Jacqz-Aigrain Evelyne
Pediatric Sleep Disorders Center, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Child and Adolescent Psychiatric Department, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Drug Des Devel Ther. 2014 Dec 1;8:2321-32. doi: 10.2147/DDDT.S65495. eCollection 2014.
Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its pharmacokinetics, short-term efficacy, and safety.
A total of 24 children (aged 9-12 years) with ADHD (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text-revision criteria) received a daily dose of 1 mg for 7 days and were followed for 3 additional weeks. Pharmacokinetic samples were collected after the first administration. ADHD symptoms were assessed using the ADHD Rating Scale (RS)-IV, Conners' Parent Rating Scale - Revised: Long (CPRS-R:L) at screening, baseline, and the end of the study. The Clinical Global Impression - Severity (CGI-S) scale was assessed at baseline, and the CGI - Improvement (CGI-I) scale was assessed at subsequent visits.
Twenty-one subjects (aged 10±1 years) were analyzed. Pharmacokinetic data were described by a one-compartment model with first-order absorption, elimination, and lag time. The typical apparent clearance and apparent volume of distribution were 27.9 L/h and 234 L, and increased with fat-free mass and age, respectively. The mean change in score in ADHD RS-IV after 1 week of mazindol was -24.1 (P<0.0001), greater than a 90% improvement from baseline. Reduction of CPRS-R:L and CGI-S scores were -52.1 (P<0.0001) and -2.5 (P<0.01), respectively. Adverse events were mild to moderate, decreased appetite and upper abdominal pain being the most common.
This preliminary study shows that mazindol might be an effective, well-tolerated, and long-acting (more than 8 hours) agent for the treatment of ADHD in children.
有人提出马吲哚可作为治疗儿童注意力缺陷多动障碍（ADHD）的一种潜在药物。本初步研究的目的是评估其药代动力学、短期疗效及安全性。
共有24名患有ADHD的儿童（年龄9至12岁，根据《精神疾病诊断与统计手册》第四版，修订文本标准），接受每日1毫克的剂量，为期7天，并随访另外3周。首次给药后采集药代动力学样本。在筛查、基线及研究结束时，使用ADHD评定量表（RS）-IV、康纳斯父母评定量表-修订版：长式（CPRS-R:L）评估ADHD症状。在基线时评估临床总体印象-严重程度（CGI-S）量表，在随后的访视中评估CGI-改善（CGI-I）量表。
分析了21名受试者（年龄10±1岁）。药代动力学数据采用具有一级吸收、消除和滞后时间的单室模型进行描述。典型的表观清除率和表观分布容积分别为27.9升/小时和234升，且分别随去脂体重和年龄增加。服用马吲哚1周后，ADHD RS-IV评分的平均变化为-24.1（P<0.0001），较基线改善超过90%。CPRS-R:L和CGI-S评分的降低分别为-52.1（P<0.0001）和-2.5（P<0.01）。不良事件为轻至中度，最常见的是食欲减退和上腹部疼痛。
这项初步研究表明，马吲哚可能是一种有效、耐受性良好且长效（超过8小时）的治疗儿童ADHD的药物。
