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 +/- 5mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >= 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.