采用渗透泵控释制剂治疗的注意缺陷多动障碍青少年的血浆哌甲酯水平
Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.
作者信息
Yorbik Ozgur, Mutlu Caner, Ozilhan Selma, Eryilmaz Gul, Isiten Nuket, Alparslan Serdar, Saglam Esra
机构信息
*Department of Child and Adolescent Psychiatry, Faculty of Medicine, Maltepe University; †Department of Child and Adolescent Psychiatry, Bakirkoy Prof Dr Mazhar Osman Training and Research Hospital for Psychiatry, Neurology and Neurosurgery; ‡Clinical Pharmacogenetic Laboratory; §Division of Psychiatry, Department of Psychology, Faculty of Humanities and Social Sciences; ¶Division of Child and Adolescent Psychiatry, Department of Child Development, Faculty of Health Science; and ‖Department of Moleculer Biology and Genetics, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul, Turkey.
出版信息
Ther Drug Monit. 2015 Jun;37(3):347-52. doi: 10.1097/FTD.0000000000000149.
BACKGROUND
There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma.
METHODS
The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay.
RESULTS
Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects.
CONCLUSIONS
Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.
背景
关于儿童和青少年口服渗透泵控释系统-哌甲酯（OROS-MPH）剂量与血浆哌甲酯（MPH）浓度之间关系的研究有限。本研究旨在探讨OROS-MPH剂量与药物血浆水平之间的关系。我们还研究了阿立哌唑、利培酮、氟西汀和舍曲林等其他药物对血浆中MPH水平的影响。
方法
筛选了100名注意力缺陷多动障碍（ADHD）患者（76名男性，24名女性）的病历，这些患者根据《精神障碍诊断与统计手册（第四版）》标准被诊断为ADHD。患者年龄在6至18岁之间（平均 = 11.5 ± 3.8岁）。采用高效液相色谱-串联质谱分析法测定血浆MPH水平。
结果
ADHD儿童使用的每日平均OROS-MPH剂量为0.7 ± 0.2 mg/kg（范围：0.3 - 1.3 mg/kg）。血浆OROS-MPH平均水平为11.6 ± 7.3 ng/mL（范围：0.5 - 43.4 ng/mL）。在使用包括阿立哌唑（n = 25）、利培酮（n = 10）、氟西汀（n = 16）、舍曲林（n = 10）在内的任何其他药物的组与未使用这些药物的组之间，血浆MPH平均水平和剂量相关的MPH水平无组间差异（P > 0.05）。OROS-MPH剂量（mg/kg）与血液MPH水平之间存在正相关（Pearson相关系数 = 0.40；P < 0.001）。65%的受试者血浆MPH水平低于13 ng/mL。
结论
我们的研究结果表明，MPH血浆水平在相似剂量下呈现广泛变化，与剂量呈正相关，并且如预期的那样，不受使用利培酮、舍曲林、氟西汀和阿立哌唑的影响。治疗药物监测可能有助于优化对治疗无反应或出现严重副作用患者的MPH剂量，但在常规临床实践中并非如此。OROS-MPH的45毫克片剂等中等剂量制剂的存在可能有助于优化治疗。
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