Psychopharmacology of Attention Deficit Disorder: Pharmacokinetic, Neuroendocrine, and Behavioral Measures Following Acute and Chronic Treatment with Methylphenidate
Despite the frequent use of methylphenidate (MPH) in school-aged children with disorders of attention, impulsivity, and activity regulation (attention deficit disorder, ADD), little is known of its clinical pharmacology. The pharmacokinetics of MPH as well as its effects on growth hormone and prolactin were examined after oral administration in 14 boys with ADD ranging in age from 7 to 12 years (mean 10.4 years). Peak concentrations determined in these acute studies were compared with concentrations obtained two hours after MPH administration in another group of children with ADD who were receiving MPH chronically. After a lag phase of approximately ? to 1 hour, MPH reached a peak plasma concentration at 2.5 ± 0.65 hours after 0.34 mg/kg and 1.9 ± 0.82 hours after 0.65 mg/kg (mean ± SD). Terminal half-lives were 2.53 ± 0.59 and 2.61 ± 0.29 hours after administration of 0.34 and 0.65 mg/kg, respectively. Observed maximal concentrations ranged from 11.2 ± 2.7 ng/ml after administration of 0.34, and 20.2 ± 9.1 ng/ml after administration of 0.65 mg/kg. The mean area under the curve after administration of 0.65 mg/kg was approximately double that calculated at 0.34 mg/kg. Plasma growth hormone increased significantly from an initial (pre-MPH) mean concentration of 4.4 to peak at two hours at 10.5 ng/ml. Prolactin concentration declined significantly from a pre-MPH level of 9.5 to a nadir at 1? hours of 3.80 ng/ml, supporting the notion that MPH is acting via central dopaminergic mechanisms. MPH concentrations in children receiving doses of 0.34 mg/kg chronically averaged 8.00 ± 0.91 at two hours, after medication, approximating the mean concentration at the same time observed in the acute study. The concentration of MPH in single "spot" samples obtained at two to three hours after administration of medication were significantly correlated with the percentage of improvement in the abbreviated Conners rating scale, indicating a relationship between plasma MPH concentration and clinical response.
展开▼
机译：尽管在注意力，冲动和活动调节（注意缺陷障碍，ADD）疾病的学龄儿童中经常使用哌醋甲酯（MPH），但对其临床药理学知之甚少。在14名ADD年龄在7至12岁（平均10.4岁）的男孩中，口服后检查了MPH的药代动力学及其对生长激素和催乳激素的影响。将这些急性研究中确定的峰值浓度与另一组长期接受MPH的ADD儿童的MPH给药两小时后获得的浓度进行比较。在大约滞后阶段？在1到1小时内，MPH在0.34 mg / kg之后的2.5±0.65小时和0.65 mg / kg之后的1.9±0.82小时达到峰值血浆浓度（平均值±SD）。给药0.34和0.65 mg / kg后，终末半衰期分别为2.53±0.59和2.61±0.29小时。给药0.34后观察到的最大浓度范围为11.2±2.7 ng / ml，给药0.65 mg / kg后观察到的最大浓度为20.2±9.1 ng / ml。给药后曲线下的平均面积为0.65 mg / kg，约为计算值0.34 mg / kg的两倍。血浆生长激素从最初的（MPH前）平均浓度4.4显着增加到两个小时（10.5 ng / ml）达到峰值。催乳素的浓度从MPH之前的9.5降至1？时间为3.80 ng / ml，支持MPH通过中枢多巴胺能机制起作用的观点。服药后两小时，接受0.34 mg / kg剂量的儿童的MPH浓度长期平均为8.00±0.91，近似于急性研究中同时观察到的平均浓度。服用药物后两到三小时内获得的单个“斑点”样品中MPH的浓度与缩写的Conners评分量表的改善百分率显着相关，表明血浆MPH浓度与临床反应之间存在关联。
展开▼
