To determine whether the difference in the pharmacokinetic profiles of IR and extended-release MPH formulations influenced driving performance throughout the day, a study was conducted to compare IR MPH dosed 3 times daily (tid) with once-daily, OROS® MPH (CONCERTA®) (Cox 2004a). OROS MPH delivers MPH via an osmotic pump to produce an ascending profile with duration of treatment effect through 12 hours(Swanson 2003). Once-daily dosing of OROS MPH is similar to IR MPH dosed tid and minimizes the fluctuations in peak and trough plasma concentrations associated with MPH dosed tid(Swanson 2003). Therefore, in this crossover study design, OROS MPH was administered at 8:00 AM, and IR MPH was administered tid at 8:00 AM, 12:00 PM, and 4:00 PM. The driving performance of adolescents with ADHD aged 16 to 19 years was assessed using a driving simulator at 2:00, 5:00, 8:00 and 11:00 PM. When subjects were administered IR MPH, simulated driving performance worsened by a factor of 5 at 8:00 PM and 11:00 PM, but driving performance in subjects receiving OROS MPH remained stable from 2:00 PM to 11:00 PM. Not only was driving performance significantly better in subjects receiving OROS MPH (P<0.001), but subjects treated with OROS MPH demonstrated significantly less variability in driving performance (P<0.001).