Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.
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.
*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.
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D000284:Administration, Oral; D000293:Adolescent; D000068180:Aripiprazole / Q000494:pharmacology; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood; D002648:Child; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000097:blood*; D012189:Retrospective Studies; D018967:Risperidone / Q000494:pharmacology; D020280:Sertraline / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D005473:Fluoxetine; D008774:Methylphenidate; D000068180:Aripiprazole; D018967:Risperidone; D020280:Sertraline