Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Stevens
Jonathan R
JR
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts 02138, USA.
George
Robert A
RA
Fusillo
Steven
S
Stern
Theodore A
TA
Wilens
Timothy E
TE
D000284:Administration, Oral; D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D009997:Osmotic Pressure; D011569:Psychiatric Status Rating Scales; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D055815:Young Adult
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate