Pharmacokinetics of methylphenidate transdermal system (MTS): results from a laboratory classroom study.
OBJECTIVE
To evaluate the pharmacokinetic properties of the methylphenidate transdermal system (MTS) in pediatric patients diagnosed with ADHD (attention-deficit/hyperactivity disorder) in a laboratory school setting.


METHODS
A phase II, randomized, double-blind, placebo-controlled, laboratory classroom study was conducted with prior dose optimization. Children (aged 6-12 years) with ADHD were titrated over 5 weeks to an optimal clinical MTS dose (10, 15, 20, or 30 mg/9 h). Participants were randomized to 1 week of either MTS or corresponding placebo, followed by crossover to the alternate treatment. Laboratory school evaluations, including pharmacokinetic blood sampling, occurred at the end of each treatment.


RESULTS
MTS delivered d- and l-MPH (methylphenidate) into the systemic circulation throughout the 9-hour wear time, and plasma concentrations declined rapidly after patch removal. Over the time-course of clinical effectiveness (2-12 h), mean plasma concentrations of d-MPH at the most frequently titrated doses (15 and 20 mg/9 h) ranged from 4.97 to 28.3 ng/mL. Systemic exposure increased approximately dose proportionately. Plasma concentrations of the l-MPH were approximately one-half to two-thirds those for d-MPH.


CONCLUSIONS
Plasma concentrations of the much less active l-MPH were consistently lower than those of d-MPH. The clinical relevance of the MTS pharmacokinetic profile is discussed.
Pierce
David
D
Shire Pharmaceutical Development Ltd, Basingstoke, United Kingdom. dpierce@shire.com
Dixon
Catherine M
CM
Wigal
Sharon B
SB
McGough
James J
JJ