Single- and multiple-dose pharmacokinetics of methylphenidate administered as methylphenidate transdermal system or osmotic-release oral system methylphenidate to children and adolescents with attention deficit hyperactivity disorder.

This was a 1-month, multicenter, open-label, randomized study to determine single- and multiple-dose pharmacokinetics of d,l-methylphenidate (MPH) after MPH transdermal system (MTS) and osmotic-release oral system MPH (OROS MPH) dosing in children (6-12 years) and adolescents (13-17 years) who had a diagnosis of attention deficit hyperactivity disorder. The pharmacokinetic population consisted of 33 children and 31 adolescents. Accumulation of d-MPH was 34% in children and 57% in adolescents after multiple fixed doses of MTS for 7 days and 76% and 94%, respectively, after 28 days of dosing. After 7 days of OROS MPH dosing, accumulation was 16% in children and 19% in adolescents; fixed doses of OROS MPH were not studied beyond 7 days. After escalating the doses to 30 mg per 9 hours for MTS, accumulation was 73% in children and 83% in adolescents after allowing for dose escalation. Corresponding values for OROS MPH after dose escalation to 54 mg were 33% in both age groups. Plasma l-MPH concentrations were approximately half those of d-MPH for MTS and negligible for OROS MPH. Overall, MTS accumulation was above that expected for single-dose pharmacokinetics of MTS and OROS MPH in both age groups. As a result of accumulation, systemic exposure to d-MPH in children after multiple escalating doses was 1.4- to 1.6-fold higher for MTS compared with OROS MPH, but similar in adolescents for both formulations. After all dosing, systemic exposure was greater in children compared with adolescents, consistent with lower body weight in children. Adverse events were mild to moderate for both formulations, and MTS dermal responses were mild.

RCT Entities:   Population Interventions Outcomes