Stevens Jonathan R, George Robert A, Fusillo Steven, Stern Theodore A, Wilens Timothy E
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts 02138, USA.
J Child Adolesc Psychopharmacol. 2010 Feb;20(1):49-54. doi: 10.1089/cap.2008.0128.
Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications.
We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment.
Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined.
Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs.
High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.
越来越多的儿童和青少年正在接受注意力缺陷多动障碍（ADHD）治疗，使用各种高于美国食品药品监督管理局（FDA）批准剂量的兴奋剂，并与其他药物联合使用。
我们试图确定接受高剂量、缓释渗透泵口服系统（OROS）哌甲酯（MPH）加用其他药物治疗的儿童和青少年体内的MPH浓度，并根据治疗的安全性和耐受性来检测MPH浓度。
在确诊为ADHD的青少年样本中，用药4 - 5小时后通过液相色谱 - 质谱法测量血浆MPH浓度。这些青少年除服用其他药物外，还接受高于FDA批准剂量的OROS MPH自然疗法治疗。同时还检测了安全性和耐受性指标（如血压和心率测量值）。
在17例患者中（平均年龄16.2±2岁，平均同时服用药物数量为2.23±0.94种），尽管OROS MPH的平均日剂量为169±5毫克（3.0±0.8毫克/千克/天），但平均血浆MPH浓度为28±9.1纳克/毫升。没有患者的血浆MPH水平≥50纳克/毫升或出现兴奋剂中毒的临床体征。血浆MPH浓度与OROS MPH剂量或生命体征变化之间未发现相关性。
高剂量OROS MPH与其他药物联合使用时，既不会导致血浆MPH浓度异常升高，也不会引起生命体征出现具有临床意义的变化。研究局限性包括MPH浓度的单时间点采样、样本量小以及缺乏评估治疗效果的结局指标。
