Single-dose pharmacokinetics of NWP06, an extended-release methylphenidate suspension, in children and adolescents with ADHD.

ABSTRACT

BACKGROUND: Extended-release formulations of stimulants provide once-daily treatment options for patients with attention-deficit/hyperactivity disorder (ADHD). Such preparations are more convenient and may improve compliance, and thus, improve outcomes. Currently, there is no extended-release liquid oral preparation of any stimulant. As such, there is a medical need for a liquid extended-release preparation of methylphenidate for the management of ADHD in children who are unable or unwilling to swallow solid formulations. OBJECTIVE: To evaluate the single-dose pharmacokinetics of an extended-release oral liquid formulation of methylphenidate (NWP06) in pediatric subjects with ADHD. METHODS: Subjects with ADHD received a single oral dose of NWP06 20 or 60 mg. Serial blood samples were obtained before and after drug administration for determination of plasma methylphenidate concentrations and standard pharmacokinetic parameters. Dose- and weight-corrected pharmacokinetic parameters were presented by age group (9-12 years and 13-15 years). RESULTS: A total of 14 youths (7 children aged 9-12 years and 7 adolescents aged 13-15 years) were enrolled and completed the study. Body mass index ranged from 12.08 to 34.08 kg/m(2). Mean values of dose and body weight-adjusted maximum plasma concentration (Cmax) (23.8, 22.3, 22.1, 25.7 [ng/mL]/mg) and area under the concentration-time curve (AUC) (208, 199, 239, 210 [hr·ng/mL]/[mg/kg]) were similar among all age/dose groups, suggesting dose proportionality and a similar rate and extent of absorption in children and adolescents. Values for Cmax were observed between 2 and 4 hours after the dose. The elimination half-life and body weight-adjusted clearance also appeared to be independent of dose and age. NWP06 was well tolerated with no serious adverse events and no adverse event-related treatment discontinuations. CONCLUSION: There were no age-related pharmacokinetic differences after oral administration of NWP06 to children or adolescents in this small sample. Over the dose range of methylphenidate used in this study (0.45-3.3 mg/kg), the pharmacokinetics of NWP06 were linear and dose proportional.