Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, NV, USA.
Postgrad Med. 2011 Sep;123(5):80-8. doi: 10.3810/pgm.2011.09.2462.
Extended-release formulations of stimulants provide once-daily treatment options for patients with attention-deficit/hyperactivity disorder (ADHD). Such preparations are more convenient and may improve compliance, and thus, improve outcomes. Currently, there is no extended-release liquid oral preparation of any stimulant. As such, there is a medical need for a liquid extended-release preparation of methylphenidate for the management of ADHD in children who are unable or unwilling to swallow solid formulations.
To evaluate the single-dose pharmacokinetics of an extended-release oral liquid formulation of methylphenidate (NWP06) in pediatric subjects with ADHD.
Subjects with ADHD received a single oral dose of NWP06 20 or 60 mg. Serial blood samples were obtained before and after drug administration for determination of plasma methylphenidate concentrations and standard pharmacokinetic parameters. Dose- and weight-corrected pharmacokinetic parameters were presented by age group (9-12 years and 13-15 years).
A total of 14 youths (7 children aged 9-12 years and 7 adolescents aged 13-15 years) were enrolled and completed the study. Body mass index ranged from 12.08 to 34.08 kg/m(2). Mean values of dose and body weight-adjusted maximum plasma concentration (Cmax) (23.8, 22.3, 22.1, 25.7 [ng/mL]/mg) and area under the concentration-time curve (AUC) (208, 199, 239, 210 [hr·ng/mL]/[mg/kg]) were similar among all age/dose groups, suggesting dose proportionality and a similar rate and extent of absorption in children and adolescents. Values for Cmax were observed between 2 and 4 hours after the dose. The elimination half-life and body weight-adjusted clearance also appeared to be independent of dose and age. NWP06 was well tolerated with no serious adverse events and no adverse event-related treatment discontinuations.
There were no age-related pharmacokinetic differences after oral administration of NWP06 to children or adolescents in this small sample. Over the dose range of methylphenidate used in this study (0.45-3.3 mg/kg), the pharmacokinetics of NWP06 were linear and dose proportional.
对于患有注意缺陷多动障碍（ADHD）的患者，缓释制剂提供了每日一次的治疗选择。这些制剂更方便，可能会提高顺应性，从而改善治疗效果。目前，尚无任何兴奋剂的缓释口服液。因此，对于不能或不愿服用固体制剂的 ADHD 患儿，需要一种液体缓释哌甲酯制剂。
评估哌甲酯缓释口服液（NWP06）在 ADHD 儿科患者中的单剂量药代动力学。
ADHD 患儿接受 NWP06 20 或 60mg 的单次口服剂量。给药前后采集系列血样，以测定血浆哌甲酯浓度和标准药代动力学参数。按年龄组（9-12 岁和 13-15 岁）呈现剂量和体重校正后的药代动力学参数。
共纳入 14 名青少年（7 名 9-12 岁儿童和 7 名 13-15 岁青少年），并完成了研究。体重指数范围为 12.08-34.08kg/m2。所有年龄/剂量组的平均剂量和体重校正后的最大血浆浓度（Cmax）（23.8、22.3、22.1、25.7[ng/mL]/mg）和浓度-时间曲线下面积（AUC）（208、199、239、210[hr·ng/mL]/[mg/kg]）值相似，提示剂量比例一致，儿童和青少年的吸收速率和程度相似。Cmax 值在给药后 2-4 小时观察到。消除半衰期和体重校正后的清除率似乎也与剂量和年龄无关。NWP06 耐受性良好，无严重不良事件和与不良事件相关的治疗中断。
在这个小样本中，儿童或青少年口服 NWP06 后没有观察到与年龄相关的药代动力学差异。在本研究中使用的哌甲酯剂量范围内（0.45-3.3mg/kg），NWP06 的药代动力学呈线性和剂量比例关系。
